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   New trials since Feb 2017 | Trial Talk:  experts to consult for second opinions | New Trials of interest
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INDOLENT LYMPHOMA TREATMENT SURVEY:
to learn about the treatments you received, were offered,
and your role in decisions

interim report | FL only | MZL only 2/5/17
 

LYMPHOMA PATIENT SURVEY
to learn about your status, experiences,
and what's important to you


Results

 
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Tissue Specimens in Clinical Trials: A Double-Edged Sword - The ASCO
Post http://bit.ly/2uMHm31
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SEER Non-Hodgkin Lymphoma - Cancer Stat Facts 1975-2014 http://bit.ly/2vI9Hel
SEER Hodgkin Lymphoma - Cancer Stat Facts - 2014 http://bit.ly/2fvgcL1
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Acalabrutinib received an FDA breakthrough designation for the treatment of Mantle Cell Lymphoma.

This designation is given when "preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development."

Here’s the (no-longer recruiting) study that’s the likely basis for the breakthrough designation:
https://clinicaltrials.gov/show/NCT02213926 

Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor | Journal of Hematology & Oncology | Full Text http://bit.ly/2vojqWv 

"Acalabrutinib (ACP-196) is a novel irreversible second-generation BTK inhibitor that was shown to be more potent and selective than ibrutinib. This review summarized the preclinical research and clinical data of acalabrutinib."

Comment: Acalabrutinib is in the same class as Ibrutinib (similar target, also an oral drug). Ibrutinib is already approved for use in MCL. So we might safely assume that the efficacy and/or safety appears to be substantially better for Acalabrutinib. However, I could not find an published reports on outcomes in the trial above - nor a statement by FDA on the basis for the decision. In any case, it's very big and good news.


Fact Sheet: FDA Breakthrough Therapies http://bit.ly/2uYNN3y 

 
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PROs in NCI clinical trials, Dr. Lori Minasian - CIRB-CPC-ePRO-2017-Lori-Minasian-MD,FACP.pdf
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Patient-Reported Outcome Alerts | Health Care Safety | The JAMA Network http://bit.ly/2f1ayQt 

The assessment of patient-reported outcomes (PROs) in clinical trials poses a number of potential problems. What happens when a patient reports a severe symptom and no one is monitoring that information; for example, when questionnaires are not reviewed until the end of a study? Do hospitals or researchers face liability if a patient reports suicidal thoughts on a questionnaire?
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Check this checkpoint inhibitor in lymphoma | Blood Journal http://bit.ly/2v3Ai5g

snip:  "The time is now ripe to devise a clinically relevant classification that would take into consideration biological features that have treatment implications. For instance, PDL-1–expressing lymphomas could be grouped together. Aside from HL and PMLBCL, this category would also include mediastinal gray zone lymphomas6 and Richter transformation of chronic lymphocytic leukemia.7 Potentially, other lymphomas could be included.

There is frequent overexpression of PD-L1 in Epstein-Barr virus as well as other virus-related lymphomas,8 which include Burkitt lymphoma, HIV-associated DLBCL, HIV-associated primary central nervous system lymphoma, Epstein-Barr virus+ posttransplant lymphoproliferative disorder, plasmablastic lymphomas, extranodal natural killer/T-cell lymphoma, angioimmunoblastic T-cell lymphoma, human herpesvirus 8-associated primary effusion lymphoma, and multicentric Castleman disease."
 
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Insurance approval rates for clinical trial participation rose under Affordable Care Act | Science News http://bit.ly/2gNJdBS
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7/14/17: Healthcare Bill -- update on BCRA by Slavitt
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Central nervous system relapse of diffuse large B-cell lymphoma in the rituximab era:
Results of the UK NCRI R-CHOP-14 versus 21 trial | Annals of Oncology | Oxford Academic http://bit.ly/2vFkhPE 

snip: Conclusion: Despite very limited use of IV MTX as prophylaxis, the incidence of CNS relapse following R-CHOP was very low (1.9%) confirming the reduced incidence in the rituximab era. The CNS-IPI identified patients at highest risk for CNS recurrence.
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JCO 2017: Lymphoma Remissions Caused by Anti-CD19 Chimeric Antigen Receptor T Cells Are Associated With High Serum Interleukin-15 Levels http://bit.ly/2ueiDH0  (full text)
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PD-1 Blockade in Mediastinal Gray-Zone Lymphoma — NEJM http://bit.ly/2sIKvjc

"The high frequency of 9p24.1 copy-number alterations across mediastinal lymphomas suggests a disease-specific, genetically determined dependence on PD-1 for survival. These cases provide early evidence for using PD-1 inhibition in relapsed or refractory mediastinal gray-zone lymphoma, which warrants further testing."
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2017, Splenic marginal zone lymphoma: from genetics to management
http://bit.ly/2tGnI8W 
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Incidence of marginal zone lymphoma in the United States, 2001–2009 with a focus on primary anatomic site
http://bit.ly/2sHpSnt 
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Bone marrow biopsies
do not impact response assessment for follicular lymphoma patients treated on clinical trials. abstract http://bit.ly/2u014Lj
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ADCT-301 – A Novel Antibody-drug Conjugate Against Lymphomas – Moves Into Phase I Clinical Trial ADC Review http://bit.ly/2sB0obj
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varlilumab
A human agonistic monoclonal antibody (MoAb) specific for CD27, with potential immunostimulating and antineoplastic activity. Upon administration of CDX-1127, this MoAb binds to CD27 and may potentiate the immune response by increasing the cytotoxic T-lymphocyte (CTL) response against CD27-expressing tumor cells. This may lead to growth inhibition of CD27-expressing tumor cells. In addition, this agent may increase the proliferation and activation of antigen-specific T lymphocytes upon co-administration of TAA-containing vaccines, such as dendritic cell vaccines. CD27, a co-stimulatory molecule and member of the tumor necrosis factor family overexpressed in certain tumor cell types, is constitutively expressed on mature T-lymphocytes, memory B cells and natural killer cells and plays an important role in NK cell mediated cytolytic activity and T and B lymphocyte proliferation and activation. Check for active clinical trials using this agent. (NCI Thesaurus)
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Ibrutinib - First Drug Approved for Marginal Zone Lymphoma http://wb.md/2u10bCf
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Background:

Immunotherapy: Using the Immune System to Treat Cancer - National Cancer Institute http://bit.ly/2tA44gT

Immune system - a video https://youtu.be/Lb-iMePZhLw

Crash course in three parts:
Immune System, part 1:
https://youtu.be/GIJK3dwCWCw 

Immune System, part 2:
https://youtu.be/2DFN4IBZ3rI

Immune System, part 3:
https://youtu.be/rd2cf5hValM
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MRD status at EOI was a sensitive marker of treatment efficacy, n the randomised GADOLIN study
http://onlinelibrary.wiley.com/doi/10.1002/hon.2438_80/full
Reminder: identifying a surrogate for benefit (viral load) fostered rapid progress against HIV.
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EZH2 alterations in follicular lymphoma: biological and clinical correlations - Europe PMC Article - full text http://bit.ly/2rP07QK
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Rituximab SC had similar efficacy and safety to the IV form
http://onlinelibrary.wiley.com/doi/10.1002/hon.2438_46/full
Grade =3 adverse events (58.3% SC; 54.3% IV)
Is safety really similar?
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Venetoclax Achieves Durable and Deep "treatment free" Remissions in CLL - The ASCO Post http://bit.ly/2tuyRcD 
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PROs: Collecting Patient-Reported Outcomes in Cancer Clinical Trials - National Cancer Institute http://bit.ly/2sIhqUs

ASCO17: Quickly reporting cancer complications (online PROs) may boost survival http://bit.ly/2rA1MLC  
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2017 ASCO Annual Meeting Abstracts http://bit.ly/2rFHX5a
Search tool
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2017: Dr. O'Brien on CLL updates at ASCO 17 https://youtu.be/OK2WMtotPws
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Survival outcomes for various treatment modalities in advanced-stage grade 3 follicular lymphoma (FL3):
A National Cancer Database (NCDB) study. | 2017 ASCO Annual Meeting Abstracts http://bit.ly/2qKJGHU
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Therapeutic CD94/NKG2A blockade improves natural killer cell dysfunction in CLL - PubMed #lymsm http://bit.ly/2pnlKqp

Studies testing Monalizumab (CD94/NKG2A checkpoint mab) for| CLL OR lymphoma http://bit.ly/2pcTCe4 

Monalizumab: anti-NKG2A mAb partnered with AstraZeneca and MedImmune | Innate Pharma http://bit.ly/2pMyom9

Monalizumab (previously IPH2201) is a checkpoint inhibitor, which is focused on re-establishing a broad anti-tumor response mediated by both NK and T cells.  Monalizumab is a first-in-class humanized IgG4 targeting NKG2A receptors expressed on tumor infiltrating cytotoxic NK and CD8 T lymphocytes.
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2017:
Targeting NK Cells for Anticancer Immunotherapy: Clinical and Preclinical Approaches. http://bit.ly/2pkoV6Y  (full text) 
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M7FLIPI: A Follicular Lymphoma Prognostic Model for the 21st Century
Ann S. LaCasce, MD, MSc  hematology.org
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Clinical Controversies of Double-Hit Lymphoma | Gotoper.com http://bit.ly/2qoLfex 
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Monalizumab (a checkpoint inhibitor):
anti-NKG2A mAb partnered with AstraZeneca and MedImmune | Innate Pharma
http://bit.ly/2pMyom9
 
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Impact of Expert Pathologic Review of Lymphoma Diagnosis:
Study of Patients From the French Lymphopath Network
full text: http://bit.ly/2oViQO7 
 
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Conflict of Interest in Medical Research, Education, and Practice - NCBI Bookshelf http://bit.ly/2pYGhlV
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What is the focus of lymphoma research in 2017?
Anas Younes
https://youtu.be/QgXcbfO_6sY 
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Production of Chimeric Antigen Receptor T cells
https://www.nature.com/nprot/posters/cart/cart_poster.pdf
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Testing Cirmtuzumab and Ibrutinib in Patients With B-Cell Lymphoma
B-cell Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Mantle Cell Lymphoma


ClinicalTrials.gov http://bit.ly/2o9dwFz 

About Cirmtuzumab
Targets ROR1 to Inhibit Ibrutinib-Resistant, Wnt5a-Induced Rac1 Activation in CLL | Blood Journal http://bit.ly/2oiiIV7
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Disparities in survival by insurance status in patients with Hodgkin lymphoma -
 Parikh - 2015 - Cancer - Wiley Online Library http://bit.ly/2k6Udsl
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Nivolumab (immune checkpoint MAb) + Brentuximab Vedotin (cd30-drug-conj)
After SCT for High-Risk Classical Hodgkin http://bit.ly/2mY9HD2
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Axicabtagene Ciloleucel (Kite CAR t-cell therapy targeting cd19)
Shows Response Rate of 76% in Aggressive Lymphoma http://bit.ly/2mEjHx2
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The number of extranodal sites assessed by PET/CT scan
predictor of CNS relapse for patients with diffuse large B-cell lymphoma: http://bit.ly/2lOsxsI
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Suboptimal dosing of rituximab in male and female patients with DLBCL. - PubMed - NCBI http://bit.ly/2kPfE34
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Clinico-biological characteristics and outcome of hepatitis C virus-positive DLBC Lymphoma http://bit.ly/2lotqXK
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CAR T-Cell Therapy KTE-C19 Appears Successful in Aggressive B-Cell Lymphoma - The ASCO Post http://bit.ly/2jLl6oJ
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Venetoclax (ABT-199) Studied in Relapsed or Refractory Non-Hodgkin Lymphoma - The ASCO Post http://bit.ly/2l4Z5Ow 
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Howard Burris, MD from Sarah Cannon, Nashville, TN discusses TGR-1202 for chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). TGR-1202 is a PI3K delta inhibitor and Dr Burris discusses how it may be the third compound in this area that will be used in the clinic next to idelalisib and IPI-145. TGR-1202 is well tolerated and is used as a single agent and in combination. Recorded at the American Society of Oncology (ASCO) 2016 Annual Meeting held in Chicago, IL.
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Studies testing TGR-1202 (next gen PI3K delta inhibitor) for #Lymphoma or #CLL ClinicalTrials.gov http://bit.ly/2jg0Aep
Video: https://youtu.be/9By-u9FIbEM
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Dr Leonard: VIDEO: R-CHOP remains standard of care in DLBCL http://bit.ly/2hJbnd1
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KTE-C19 (anti-CD19 CAR T Cells) in Chemorefractory
Primary Mediastinal B-Cell Lymphoma & Transformed Follicular
http://bit.ly/2fDsqNk 

Ibrutinib-Lenalidomide-Rituximab in R/R Mantle Cell Lymphoma: First Results from the Nordic Group http://bit.ly/2fTTQxE 

Continued Excellent Outcomes in Previously Untreated Follicular Lymphoma Patients after Treatment with CHOP Plus Rituximab or CHOP Plus (131) Iodine-Tositumomab - Long Term Follow-up of Phase III Randomized Study SWOG S0016 http://bit.ly/2fsnuO7 

Intervention Versus Observation: What Is the Appropriate Endpoint?
Assessment of Endpoints in Patients with Advanced Stage Follicular Lymphoma Who Are Initially Observed http://bit.ly/2fGWonI 

Obinutuzumab-Based Induction and Maintenance Prolongs Progression-Free Survival (PFS) in Patients with Previously Untreated Follicular Lymphoma: Primary Results of the Randomized Phase 3 GALLIUM Study http://bit.ly/2fMEhMn 

Minimal Residual Disease in Patients with Follicular Lymphoma Treated with Obinutuzumab or Rituximab As First-Line Induction Immunochemotherapy and Maintenance in the Phase 3 GALLIUM Study http://bit.ly/2fqgRrP 

Polatuzumab Vedotin Combined with Obinutuzumab for Patients with Relapsed or Refractory Non-Hodgkin Lymphoma:
Preliminary Safety and Clinical Activity of a Phase Ib/II Study http://bit.ly/2fFG86e 

Paper: Rituximab Plus Lenalidomide Versus Rituximab Monotherapy in Untreated Follicular Lymphoma Patients in Need of Therapy. First Analysis of Survival Endpoints of the Randomized Phase-2 Trial SAKK 35/10 http://bit.ly/2eAp2UZ
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Medscape 2016
Bendamustine? Toxicity in FL Raises Eyebrows -- and Questions
http://wb.md/2hNXgEB
 
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Obinutuzumab-Based Induction and Maintenance Prolongs Progression-Free
Survival (PFS) in Patients with Previously Untreated Follicular Lymphoma: Primary
Results of the Randomized Phase 3 GALLIUM Study http://bit.ly/2fMEhMn

GAZYVA® (obinutuzumab) full prescribing document
https://www.gene.com/download/pdf/gazyva_prescribing.pdf
The GAZYVA dose for FL is 1000 mg

The Rituxan dose is 375 mg/m2
How do these compare - actual dose in average person?
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Obinutuzumab-Based Induction (given at 1000 mg) and Maintenance Prolongs Progression-Free
Survival (PFS) in Patients with Previously Untreated Follicular Lymphoma: Primary
Results of the Randomized Phase 3 GALLIUM Study http://bit.ly/2fMEhMn

Commentary search:
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Rituximab serum concentrations (given at 350 mg) during immuno-chemotherapy of follicular lymphoma
correlate with patient gender, bone marrow infiltration and clinical response http://bit.ly/2hiPiVd

The results of this pilot trial suggest that more differentiated dosing schedules based
on gender and bone marrow infiltration should be explored for rituximab therapy for lymphoma.
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*Medscape 2016
Bendamustine? Toxicity in FL Raises Eyebrows -- and Questions http://wb.md/2hNXgEB

(Important read for patients and oncologists)
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Positive Results from phase 2 study of rituximab, bendamustine and cytarabine (RBAC500)
as induction therapy in elderly patients with MCL | LymphomaHub http://bit.ly/2hCeRP2
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Results (encouraging) for phase II study of rituximab plus lenalidomide
for mucosa-associated lymphoid tissue Lymphoma (MALT)
... Europe PMC http://bit.ly/2hyuqqm 
 
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Financial Toxicity of Cancer
Challenges and Opportunities  EAB-financial toxicity-121316.pdf

Gary C. Doolittle, MD
Capitol Federal Masonic Professor of Oncology
Medical Director, Midwest Cancer Alliance
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The Open Notebook – Helen Ouyang Studies the Ethics of Compassionate Drug Use http://bit.ly/2hirxNl
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Our letter to ASCO Post: Limited Access to Radioimmunotherapy in Community Setting
May Lead to Extinction of a Unique Lymphoma Treatment http://bit.ly/2cOp48Z 
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Technical for scientists:
The current status of biomarkers for predicting toxicity - Europe PMC Article - Europe PMC http://bit.ly/2eoVOsT
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Why Care About the Caregivers? an underserved and undervalued group- The ASCO Post http://bit.ly/2eXcARd 
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Integrative systems to identify molecular targets in lymphoid malignancies http://bit.ly/2ctrDiS 
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ASH 15: Immunotherapy for Lymphoma Using T Cells Targeting Multiple Tumor Associated Antigens http://bit.ly/2ctiFSC
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Advocacy perspective: Ownership of Drugs Comes with Unique Responsibilities
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Refinement of the Lugano classification response criteria for lymphoma in era of immunomodulatory therapy http://bit.ly/2c61Koc

Posted to PAL topic: Response, Remission ... Terminology

Considering this finding as Progressing Disease (PD) could lead to patients being prematurely removed from a treatment from which they actually stand to benefit. This phenomenon has been well described with checkpoint blockade therapy in solid tumors, and anecdotally seen in lymphoma as well. To address this issue in the context of lymphoma immunomodulatory therapy, a workshop was convened to provide provisional recommendations to modify current response criteria in patients receiving these and future agents in clinical trials. The term "Indeterminate Response" (IR) was introduced in order to identify such lesions until confirmed as flare/pseudo-progression or true PD by either biopsy or subsequent imaging.
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Aug 2016: Dr. Julie, Brahmer,
Excellent presentation on Immunotherapy Biomarkers and Patient Selection -
YouTube http://bit.ly/2bMiIao  Posted to Biomarkers
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Scoop: Novartis disbands its pioneering cell and gene therapy unit – ENDPOINTS http://bit.ly/2bCDb2A

Sad.  Is this a marketing issue... like can CART be applied in community setting where 80% of patients are diagnosed and treated?
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Draft:  New PAL topic on mandating biopsies for research
Biopsies - perspective on mandating for research
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GADOLIN and the Perplexing Role of Obinutuzumab (cd20 antibody) in the Treatment of B-Cell Malignancies -
The ASCO Post http://bit.ly/2bzpkGW
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PAL topic updated Myths About Cancer
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Financial Toxicity and Cancer Treatment (PDQ®)—Health Professional Version -
National Cancer Institute http://bit.ly/2bxFhmW  posted to Financial Toxicity
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Poly(ADP-ribose) polymerase inhibitors combined with external beam and
radioimmunotherapy to treat aggressive lymphoma http://bit.ly/2bYNix2 

Posted to : Rationale for continued study of Radioimmunotherapy
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Testing safety of TGR-1202 (PI3K-delta Inhib) and
Ibrutinib (btk-inhib) for R&R Diffuse Large B-Cell Lymphoma http://bit.ly/2bRW6po
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PAL Topic updated: 
Encouragement for science- and evidence-based reasons to be hopeful.
 
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Cancer Vaccines: Are They the Wave of the Future? : Oncology Times http://bit.ly/2blp13O

Types of vaccines and challenges described
 
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2016 - stunning trend described, alarming
Medicare Part B Drug Reimbursement Program Distresses Pharmacy Players http://bit.ly/2aCFmpd

Medicare spent $22 billion on Part B drugs in 2015.
In 2007, the total payments were $11 billion; the average annual increase since 2007 has been 8.6%.

 
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PAL Update:
About Settings - our unique clinical circumstance
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Indolent B-cell and MCL: practical management of adverse events (AEs) -
induced by lenalidomide in monotherapy or in combination with rituximab (R2) | LymphomaHub http://bit.ly/2aj8EGA
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Dr. Vicki Morrison:
Assessment of Fitness, Function, and QOL Essential for Older Patients With CLL - The ASCO Post http://bit.ly/2aAWGpT 
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Roche - Roche provides update on phase III study of Gazyva/Gazyvaro in people with previously untreated diffuse large B-cell lymphoma http://bit.ly/2abwJAM 

CHOP-R apparently still on top for this indication.
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CHOP Chemotherapy Followed by (now extinct Bexxar)
Tositumomab and Iodine-131 Tositumomab for Previously Untreated DLBCL http://bit.ly/29RtvBs
 
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2016: Open questions in watchful waiting for follicular lymphoma - Sorigue - 2016 - BJH - http://bit.ly/29wtinq

Snip: "Admittedly, the information available (such as the intent of the treating physician) in retrospective series is often limited, but we believe that it is essential that different definitions of WW be kept in mind when comparing the results obtained in different series. At the same time, the fact that, despite different populations, no study has found an increased OS with any active treatment strategy over WW seems to make WW a very valid therapeutic option for asymptomatic patients with FL in the immunochemotherapy era."
 
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Jan 2016: Impact of the National Cancer Institute Community Cancer Centers Program on Clinical Trial
and Related Activities at a Community Cancer Center in Rural Nebraska.  http://1.usa.gov/1XtO3ke 

Although 85% of patients with cancer are diagnosed and treated in the community setting, only 3% are enrolled onto clinical trials. Lack of adequate time, infrastructure, resources, incentives, and reimbursement adversely affect clinical trial participation.
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Unmet need:
Open Studies for Richter's - ClinicalTrials.gov http://bit.ly/29AdEsg
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Continued Risk of Relapse Independent of Treatment Modality in Limited-Stage Diffuse Large B-Cell Lymphoma: Final and Long-Term Analysis of Southwest Oncology Group Study S8736 http://bit.ly/29BJaFW 

Question: Might late relapses be a second occurrence? Can original and relapse samples be evaluated to look for this?
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Dr. Zelenetz on use of Rituxan - For what indications? How much is too much?
https://youtu.be/LY9Ls64M-ak 
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study of interest - targeting a validated immune-pathway target in novel

Testing CA-170 (small molecule, Oral PD-L1, PD-L2 and VISTA Checkpoint Antagonist) for advanced cancer and #Lymphomas http://1.usa.gov/28W6he3 
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2016, June:
Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin’s Lymphoma — NEJM http://bit.ly/2903YE7

The principal aim of this trial was to determine whether an interim FDG-PET scan could be used to guide the de-escalation of therapy for patients with a high probability of cure after ABVD therapy and escalation for those at higher risk for treatment failure. The intention was to reserve more intensive treatment for patients whose poor prognosis justified the added risk. The overall results of this approach appear favorable as compared with those of our previous studies that involved full-course ABVD and more consolidation radiotherapy.5,6 This trial population as a whole had a progression-free survival rate of 82.6% (83.7% among patients <60 years of age), and only 78 of the 1203 patients (6.5%) received radiotherapy, as compared with a progression-free survival rate of 75% and 80% in the two preceding trials, in which consolidation radiotherapy was given in 38% and 53% of patients, respectively. In all these studies, patients with stage II disease but systemic symptoms or other adverse features were included, because standard care is usually with a full course of chemotherapy, but it is evident that the results in this group are generally better than in patients with stage III and IV disease.
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Risk Factors and Outcomes for Patients With Follicular Lymphoma Who Had Histologic Transformation (HT) After Response to First-Line Immunochemotherapy (rituxan-chemo) in the PRIMA Trial PDF full report 

An important report with some surprising (to me) findings, such as CR response (judge by imaging) is not associated with a decreased risk of histologic transformation (HT) at recurrence, but early relapse is -- as is presentation in a new area.

The encouraging news is that this risk is low overall (among all who responded to r-chemo) at about 2% and that only 22% relapsed within 6 years (if I have it right); and that this is 1% less than incidence of HT previously reported ... perhaps an indication that Rituxan decreases the risk of HT.

Among those who relapse early (within 1 year), 36% had HT (among those who had a biopsy to determine this). Persons with HT can benefit from high dose chemo with auto transplant; but no advantage was seen for auto SCT for those with relapse to non-transformed (regular) FL. Among these persons (relapsed to regular FL), only 10% had radioimmunotherapy compared to 33% auto SCT. Will this finding lead to more RIT and less auto SCT for first relapse to regular FL?

An important take-home point is that a biopsy at relapse is highly recommended to inform next treatment on relapse of FL after first line R-chemo (immuno-chemotherapy)

KarlS

 
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URCC NCORP nationwide randomized controlled trial investigating the
effect of exercise on chemotherapy-induced peripheral neuropathy in 314 cancer patients.
2016 ASCO Annual Meeting | Abstracts | Meeting Library http://bit.ly/28J5ZS5 
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Market Forces Cited in Lymphoma Drugs’ Disuse - The New York Times http://nyti.ms/1OunaeC

An effective treatment for lymphoma may vanish from the market - Yahoo Finance http://yhoo.it/1S97UOT
 
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Blood Journal | Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia http://bit.ly/24QYmC7
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Blood Journal | The 2016 revision of the World Health Organization classification of lymphoid neoplasms http://bit.ly/20fQVjP
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Studies testing AGS67E (anti-cd37 antibody-drug conjugate) for lymphoma - - ClinicalTrials.gov Find Trials

A first in human report: anti-CD37 antibody-drug conjugate AGS67E in #lymphoma | 2016 ASCO http://bit.ly/25cvcQG 
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Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies -
Europe PMC Article - full text http://bit.ly/1TFgYML 

Snip:

Chimeric antigen receptor T (CAR-T) cell therapy has produced promising results in clinical trials but has been challenged by the inability to control engineered cells once infused into the patient. Here we present a generalizable method of controlling CAR-T cells using peptide-engrafted antibody-based molecular switches that act as a bridge between the target cell and CAR-T cell. We show that switches specific for CD19 govern the activity, tissue-homing, cytokine release, and phenotype of switchable CAR-T cells in a dose-titratable manner using xenograft mouse models of B-cell leukemia. We expect that this method of tuning CAR-T cell responses will provide improved safety and versatility of CAR–T-cell therapy in the clinic.
 
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Draft: What is true in clinical science?  What is true?
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Hodgkin
ABVD8 and BEACOPP4+4 resulted in similar EFS and OS in high-risk advanced-stage Hodgkin HL. http://bit.ly/1SCaAcD 
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Chemo brain article:
Study Finds No Association Between Anthracycline-Based Chemo and Cognitive Decline in Women With Breast Cancer - http://bit.ly/1rOU1Rk 
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Targeted agents for lymphoma
Testing agents targeting EZH2 for Lymphoma OR CLL - ClinicalTrials.gov http://1.usa.gov/1TphnlY 

Related article:
New investigational compound shows promise against melanoma, lymphoma http://bit.ly/24ufhgi 
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Health care reform?   See background articles and general (non-partisan) advice about how to inquire about policy proposals.
Articles on Health Care Reform in the US
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Saving Access to Zevalin in the Community Setting   Sign our Letter   

As a patient group we appreciate that  protecting your privacy is important to you: 
The names of persons endorsing our letter will be keep confidential and limited to being attached to the letter we will send to the Senate committee with oversight over the NRC.  The names will not be posted and will be deleted once the letters are sent.  We do not ask for your street address or email when showing your approval for our letter.  Guarantees of privacy, however cannot be given due to the limitations of the Internet. 
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Dual HDAC, PI3K Inhibitor (CUDC-907) Active in DLBC Lymphoma and Transformed http://bit.ly/1Vkeycp

snip: Five of 37 patients evaluable for response achieved an objective response to CUDC-907. There were two complete responses and three partial responses. According to the researchers, all five of these responses were in patients with DLBCL, three of which were in patients with transformed follicular lymphoma DLBCL. Fifty-seven percent of patients had stable disease, including patients with Hodgkin lymphoma and multiple myeloma.

PAL query:
CUDC-907 (dual inhibitor of PI3K and HDAC) Find Trials
 
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FL - circulating DNA testing for lymphoma

* Dynamic monitoring of circulating tumor DNA in non-Hodgkin lymphoma. - PubMed - NCBI http://1.usa.gov/1NfE53H abstract

We
have high hopes for this approach to monitoring -- that it can be more sensitive than imaging and less burdensome (a blood sample), and one day it can be used as a way to monitor disease status and duration of response to treatment - helping to assess and compare protocols with better accuracy.

* Related clinical trials http://1.usa.gov/1e5tulj

* Dynamic monitoring of circulating tumor DNA in non-Hodgkin lymphoma. - PubMed - NCBI http://1.usa.gov/1NfE53H abstract
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2 items for Hodgkins added to lymphomation

Balancing the Risk-Benefit Ratio in the Treatment of Patients With Advanced-Stage Hodgkin Lymphoma http://bit.ly/1qxVUAs 

"In summary, the SWOG S0816 study shows that treatment intensification with BEACOPP-e in patients with HL who are PET positive after two cycles of ABVD clearly improves PFS. This result will create new opportunities for risk-adapted treatment of patients with advanced-stage HL. Other future options in this setting include incorporating targeted drugs or checkpoint inhibitors. Smarter combinations of drugs along with PET-guided treatment will likely allow maintenance of high efficacy levels as has been observed with BEACOPP-e and improved tolerability. "

Response-Adapted Therapy for Stage III to IV Hodgkin Lymphoma Using Early Interim PET Imaging: SWOG S0816 http://bit.ly/1Se0Bqw
 full text JCO 

"Although the results of SWOG S0816 argue strongly for a response-adapted approach for advanced-stage HL using early interim FDG-PET/CT, it must be acknowledged that the outcomes are being compared with historical figures with their inherent limitations.

Longer follow-up is essential for confirming that the reported findings will stand the test of time. The results of ongoing, randomized, phase III trials testing this hypothesis are needed. Finally, some treatment failures were observed, even in PET2-negative patients, which indicates that interim PET is not a perfect test. We hope that in the future, molecular biomarker studies at initial diagnosis, or the combination of biomarkers and molecular imaging may define patients who require more intense therapy with eBEACOPP or other novel targeted drugs with greater accuracy than are achievable with current technology.20 Until that time, our results suggest that the response-adapted strategy of increasing treatment to eBEACOPP in PET2-positive patients is a reasonable option for advanced-stage HL therapy"
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Medscape 2016:
Venetoclax (abt-199) Approved in US for Certain CLL Patients http://wb.md/1qKFTIh 

Venetoclax (Venclexta, AbbVie and Genentech) is indicted for use in CLL patients with the chromosomal abnormality 17p deletion who have been treated with at least one previous therapy.

In this trial, conducted in 107 CLL patients harboring the 17p deletion, who have the worst prognoses, the new drug achieved an overall response rate of 79.4%. A year later, response was maintained in most patients (84.7%). "This is a very special population with the most dismal outcome," lead author Stephan Stilgenbauer, MD, from the University of Ulm, Germany, reported at the meeting.

Comment:  Good news!  Apparently an accelerated FDA approval (conditional) - based on a single-arm study in a population with an unmet need.
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Weill Cornell 2016:
Obinutuzumab Approved by the FDA for Combination Treatment of Patients with Follicular Lymphoma http://bit.ly/1oHqMNA 

This review describes a concern with the study design -- the control group protocol, which did not include Rituxan.
 
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Drug costs:
Medicare plan on payment for cancer drugs stirs battle - Chicago Tribune  http://trib.in/23EWmLL
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The Value of PET/CT in Detecting Bone Marrow Involvement
in Patients With Follicular Lymphoma http://1.usa.gov/1S2dw0T full text (a bit technical)
 
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Study of 3 drug combination (all from same sponsor)
For Relapsed / Refractory follicular lymphoma or DLBCL
Testing GAZYVA® (anti-cd20) with
Polatuzumab Vedotin (anti-CD79b Antibody-Drug Conjugate) with
Atezolizumab (anti-PDL1 - an immune checkpoint inhibitor)
http://1.usa.gov/1VFqAeU

Background: Safety, activity of anti-CD79B antibody–drug conjugate polatuzumab vedotin in
r/r B-cell lymphoma and CLL- The Lancet http://bit.ly/23kQSZO
 
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PAL pick - study of interest for Untreated Follicular Lymphoma, without a current need to treat
Testing Rituximab With or Without Zevalin Open  
Clicks as of 4/6/16:  New  Today: >


Related topic:  Radioimmunotherapy - a snapshot of its unique properties
advocating for routinely informing patients about this choice  PAL

Related advocacy:  Letter that you can endorse -- to educate Senators about
rule change that will limit access to radioimmunotherapy in community setting
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Pal Pick - study of interest:
Testing Sequential Intranodal Immunotherapy + Anti-PD1 (Pembrolizumab) in
Follicular Lymphoma http://1.usa.gov/22CxnbA

See also: PD-1/L immune checkpoint blockade Find trials
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Low Income Is a Barrier to Clinical Trial Enrollment,
Study Suggests - National Cancer Institute http://1.usa.gov/1RhXuwm
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Added to our Neuropathy resource:
Natural products & complementary therapies for chemo-induced peripheral neuropathy: -
Abstract - Europe PMC http://bit.ly/1UbldVg  | Full text - PDF 
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8-fold increase in required training (from 80 hours to 700) needed to authorize
the administration of Zevalin is a barrier to patient access. Print version - PDF
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Lymphomatous Meningitis in
Primary Central Nervous System Lymphoma http://wb.md/1SlZkBi
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To be added: Blood Journal 
How I treat adult T-cell leukemia/lymphoma http://bit.ly/1TD2DUv
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2013 report on RCT study of mogamulizumab (KW-0761) plus VCAP-AMP-VECP
for newly diagnosed aggressive adult ATL http://bit.ly/1p1jWU7
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Advanced Clinical Cell Processing Technologies for Adoptive Memory T Cell Therapy
(2016 AAAS February 2016)) http://bit.ly/1Kt6thv 

Media report: Memory cells enhance strategy for fighting blood cancers |
Science News http://bit.ly/1Kt6TV9 
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ENCOURAGING Report on YM155 (survivin inhibitor) plus rituximab
in relapsed aggressive B-cell lymphoma

See also YM155 (Survivin inhibitor)  Find Trials >
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Suggested Trial types by clinical circumstance - proposals for researchers

A | B | C | D | E | F | G | H | I | J | K | L | M | NO | P |
 Q | R | S | T | U | V | W | X | Y | Z

 
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Draft - recipe for progress - unsolicited advice from patients to the research community
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Is Shared Decision Making a Utopian Dream
or an Achievable Goal? - The Patient, Springer  - full text http://bit.ly/1PHGzDo
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Important paper:
Clinical impact of molecular features in diffuse large B-cell lymphoma and follicular lymphoma
Julia R. Pon1 and Marco A. Marra1,2

https://t.co/1vgm9l4YUE 
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PAL's Picks - of trials to consider - many new trials and queries added
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Dr. Saltz: The Value of Considering Cost, and the Cost of Not Considering Value http://bit.ly/1OqLOWz
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FACTIT.org PRO Questionnaires http://bit.ly/20IYCng
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Clinical trial reporting failures can harm research, patients
With comment by Karl Schwartz, president of PAL, included in the article
 

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Testing MDV9300 (anti-pd-1) in R/R Diffuse Large B-cell Lymphoma (DLBCL) including transformed
 

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Atezolizumab / MPDL3280A (is a pd1-antibody)
An immune checkpoint inhibitor that blocks the breaks on the immune system

Studies testing Atezolizumab - List Results - ClinicalTrials.gov Find Trials 

Testing Atezolizumab (pd-1 antibody) with Obinutuzumab (anti-cd20) with Lenalidomide in
Relapsed / Refractory Follicular Lymphoma Trial of Interest

A related article:
New on Cancer Currents: Checking in on Cancer Checkpoint Inhibitors http://1.usa.gov/1OoFtuB 


https://twitter.com/Lymphomation
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Testing JCAR017 (CART 19) in B-cell NH Lymphoma (NHL) - Biopsy-proven refractory after frontline chemo-immunotherapy http://1.usa.gov/1TScjZ9  

Relapsed or refractory B-cell NHL, including

Diffuse large B-cell lymphoma (DLBCL) and
DLBCL not otherwise specified (NOS)
Transformed DLBCL from indolent histology (tDLBCL) and

Follicular lymphoma Grade 3B.
 

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Programming T-cells to fight lymphoma and CLL  PAL
We've added a Trial Finding query to include CARS that target other antigens (cd20, cd22 and cd19)
We've added links to recent reports at ASH and a review article published Dec 2015
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Top institutions not reporting clinical trial results as required http://bit.ly/1RmvwnY

“Stanford University, Memorial Sloan Kettering Cancer Center, and other prestigious medical research institutions have flagrantly violated a federal law requiring public reporting of study results, depriving patients and doctors of complete data to gauge the safety and benefits of treatments, a STAT investigation has found.
The violations have left gaping holes in a federal database used by millions of patients, their relatives, and medical professionals, often to compare the effectiveness and side effects of treatments for deadly diseases such as advanced breast cancer.
The worst offenders included four of the top 10 recipients of federal medical research funding from the National Institutes of Health: Stanford, the University of Pennsylvania, the University of Pittsburgh, and the University of California, San Diego. All disclosed research results late or not at all at least 95 percent of the time since reporting became mandatory in 2008.”

Comment:  Wishing these tidings were glad. Hopefully, providing sunlight on the problem will lead to better adherence. Publishing trial results is an important rule as can inform patient decision making and the conduct of future research. Publishing the results also shows respect to the participants of the clinical trials.

 
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Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia — NEJM http://bit.ly/1IHaePm
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EZH2 inhibitors  Dr. Melnick describes in video (epigenetic)   Find Trials
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New query added to Trials of Interest - PAL's Picks
Open controlled (potentially practice changing) studies for:
All Lymphoma OR CLL | CLL | Follicular | DLBCL | MCL| MZL | T-cell | WM
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DRAFT:
Proposing reimbursement for study participation
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DRAFT: 
An Advocate's Perspective on Participation in Phase I Trials  
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Incidence of Hypogammaglobulinemia in Pts Receiving Rituximab and Use of IV Immunoglobulin for Recurrent Infections http://1.usa.gov/1I0ihGA
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ASH: Ublituximab (anti-cd20) + TGR-1202 (PI3Kδ inhibitor) Demonstrates Activity and a Favorable Safety Profile in Relapsed/Refractory B-Cell NHL and High-Risk CLL: Phase I Results http://bit.ly/1Ygo0vX  

Related study of interest:
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ASH: Phase II Trial of Ofatumumab (next gen cd20 antibody- GA-101 or Gazyva) in
Previously Untreated Follicular Lymphoma CALGB 50901 (Alliance) http://bit.ly/1HKbgnL

Comment: Important finding, but not what was hoped for. Ofatumumab was expected to be a significant improvement over Rituxan. This study does not support this ... at least for follicular lymphoma. The silver lining is that this finding might serve to hold down the cost of Rituxan which remains the standard and is soon to be off-patent.  The findings will also guide future research.
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Study of interest
Testing KTE-C19 (CAR t19) in Relapsed/Refractory Mantle Cell Lymphoma (MCL) http://1.usa.gov/1M4Nebh  
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PAL topic: Settings (indications):  our unique clinical circumstance
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Nov 2015: 
NEPA
Added to ASCO Guidelines on Antiemetic (anti-nausea) Use http://wb.md/1HwV0Xj
 
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A phase I/II multicenter, open-label study of the oral histone deacetylase inhibitor Abexinostat in relapsed/refractory lymphoma. - PubMed | Full report | Results | Find trials

Very encouraging results, particularly for follicular lymphoma
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Trial of interest:
Testing Duvelisib (IPI-145) With Rituximab (R) & Bendamustine (B) vs BR +Placebo relapsed Indolent NH #Lymphoma - http://1.usa.gov/1GksTzo
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Melnick:
Figuring out how a genetic mutation implicated in non-Hodgkin lymphoma drives disease
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PAL update:
Quality of Life and other Patient Reported Outcomes
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Novel new study drug:
Testing IPH2201 (checkpoint inhibitor) With Ibrutinib for Relapse or Refractory CLL

Background:
checkpoint inhibitor - IPH2201: first-in-class anti-NKG2A mAb | Innate Pharma
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PAL study of interest:
Testing Pembrolizumab (pd1 antibody)with R-CHOP for Previously Untreated DLBC -
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PAL study of interest:
Testing Idelalisib With BI 836826 (anti-cd37) in
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PAL study of interest:
Testing Selinexor and Ibrutinib in Relapsed or Refractory Chronic or Aggressive NH -   (transformed FL are also eligible)
 
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Selinexor, a selective inhibitor of nuclear export (SINE), is enhanced through combination with standard therapies
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Farrukh T. Awan, MD
How I Manage Relapsed Chronic Lymphocytic Leukemia #CLL http://bit.ly/1QvkY2I
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Role of consolidation with yttrium-90 ibritumomab tiuxetan (Zevalin) in patients with advanced-stage follicular lymphoma http://1.usa.gov/1UQFGQB 
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Rational for sequential targeting of Bruton tyrosine kinase and Bcl-2 to overcome resistance in mantle cell lymphoma http://1.usa.gov/1FCSZb9
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Troubling: NHS England to De-List More Blood Cancer Agents in Preparation for New Drug Provision System in 2016 http://bit.ly/1VQWX9a
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Background and video on Selective BCL-2 Inhibitor (venetoclax) | BioOncology http://bit.ly/1O122KO
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Immune Response, Toll Like Receptors (TLR) Pathway - animation http://bit.ly/1JQFwOJ
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DLBCL patients who are event-free at 24 months after treatment
have a normal life expectancy. http://1.usa.gov/1UHvDb8 
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Alvarez et al. CLML 2014
What Determines Therapeutic Choices for Elderly DLBCL Pts? [Portugal] 

CONCLUSION:  This was the first characterization of the clinical care of elderly Portuguese patients with DLBCL. We showed that R-CHOP is effective even in patients > 79 years, emphasizing that treatment decisions based on age alone can compromise treatment efficacy and outcome in fit patients.
 
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NCI
Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events
brochure PRO-CTCAE.pdf
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2015, technical:
Blood Cancer Journal - Whole-exome analysis reveals novel somatic genomic alterations associated with outcome in immunochemotherapy-treated diffuse large B-cell lymphoma http://bit.ly/1JHlxB1 (full paper)
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United States Statistics released
You can find interesting relationship between state versus national averages for various cancer types.
 
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Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance) http://bit.ly/1hfqhXU 
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2015 Blood Journal
Engineered T cells CAN fight malignant T cells http://bit.ly/1Udu30z  more study needed however.
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CAR T-cell therapy:
The role of physical barriers and immunosuppression in #lymphoma: http://ow.ly/RjiUT 
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Aug 2015:
Blood Journal | Cell-of-origin of transformed follicular lymphoma http://bit.ly/1fGoVnS

We report that the expression of IRF4 is an independent predictor of early transformation (hazard ratio 13.3, P < .001). We also show that composite histology at the time of transformation predicts favourable prognosis.
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Update:  Research Advocacy topic
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Testing Anti-ICOS (MEDI-570) in Peripheral T-cell Lymphoma Follicular Variant or Angioimmunoblastic T-cell #Lymphoma http://1.usa.gov/1MwTcCu

Related background: B Cells in Health and Disease – Leveraging Flow Cytometry to Evaluate Disease Phenotype and the Impact of Treatment with Immunomodulatory Therapeutics http://bit.ly/1EAIe8L

Recent advances in T cell immunology have identified a specialized subset of CD4 T cells that provide help to B cells attempting to form a germinal center. This population has been called T follicular helper cells (TFH) (Crotty, 2011). Naïve CD4 T cells become activated in the T cell zone of the secondary lymphoid organ. The inducible costimulator, ICOS, is expressed, and ICOS engagement drives the upregulation of CXCR5 and BcL6, migration toward the B cell zone and differentiation into a TFH (Choi et al., 2011).
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Aug 2015 - from Lancet:
Integration of gene mutations in risk prognostication for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in population-based registry - http://bit.ly/1Jfpnp8

authors comment: "a promising approach to identify the subset at highest risk of treatment failure."

We established a clinicogenetic risk model (termed m7-FLIPI) that included the mutation status of seven genes (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, and CARD11), the Follicular Lymphoma International Prognostic Index (FLIPI), and Eastern Cooperative Oncology Group (ECOG) performance status.

In the training cohort, m7-FLIPI defined a high-risk group (28%, 43/151) with 5-year failure-free survival of
38·29% (95% CI 25·31–57·95) versus
77·21% (95% CI 69·21–86·14) for the low-risk group
(hazard ratio [HR] 4·14, 95% CI 2·47–6·93; p<0·0001

Put another way (if we have it right): 
1 in 3 patients in the high risk group (defined by m7-FLIPI) did well at 5-years, compared to
3/4 in the low risk group.  This finding, if validated or accepted as reproducible can be used to select patient with high risk FL for tests of novel treatments as initial treatment ... with the goal of changing the natural history of high risk FL (previously defined after relapse).
 
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Study of interest for CNS Lymphoma, primary
Testing: Ibrutinib and Immuno-Chemotherapy Using
Dose-Adjusted Temozolomide, Etoposide, Doxil, Dexamethasone, Ibrutinib, Rituximab (DA-TEDDI-R)

Patients Summary | Trial Summary (PDF)

Location: National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892 |  call
888-624-1937      

Clicks as of 8/14/15: 
New Today: >

 

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PAL update
limitations of Animal models in predicting successful new treatments
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PAL update to Patient Reported Outcomes topic:
Placebo effect on patient reported outcomes in cancer trials
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PD1 ligand associated with poor overall survival in patients with diffuse large B-cell #lymphoma. - PubMed - NCBI http://1.usa.gov/1gmMumj added to topic page
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The ASCO Post:
Study Finds Exercise in Adolescence Linked to Reduced Mortality From Cancer and All Causes http://bit.ly/1gIlFtA 

Comment:  A complementary practice to endorse, wholeheartedly. I can’t think of another besides a healthful and varied diet. The rub, there is nothing to buy or make a profit from – no side effects to treat, if done within our limits. In this case, no hype about magical natural formulae.
 
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Study of interest - relapsed indolent lymphoma:
Testing Ibrutinib / placebo With Either Bendamustine-R or CHOP-R for Previously Treated Indolent non-Hodgkin lymphoma http://1.usa.gov/1Ht0c2L

From protocol: "This is a randomized (individuals assigned to study treatment by chance), double-blind (individuals and study personnel will not know the identity of study treatments), placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial)-controlled study in approximately 400 adult participants with follicular lymphoma or marginal zone lymphoma.

... All participants will receive 6 cycles of background immune-chemotherapy with either BR or R-CHOP in combination with either placebo (Arm A) or ibrutinib (Arm B). Selection of background immune-chemotherapy will be based on prior treatment history and cardiac function.

After completion of background immune-chemotherapy, study drug (ibrutinib or placebo) will continue until disease progression, unacceptable toxicity, or study end, whichever comes first. Assessment of tumor response and progression will be conducted in accordance with the Revised Response Criteria for Malignant Lymphoma. Serial pharmacokinetic (study of what a drug does to the body) blood samples will be collected. Safety will be assessed throughout the study.
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Study of interest for previously untreated follicular lymphoma
Efficacy of Response-adapted Strategy in Follicular Lymphoma - ClinicalTrials.gov http://1.usa.gov/1h7MjMr
Purpose: "Recently, the availability of Rituxan has substantially changed therapeutic approach to FL patients, since its combination with chemotherapy has improved response rates, progression free survival (PFS) and overall survival (OS). Based on the results of recently completed randomized studies the standard treatment for patients with FL should consist of an initial therapy with R-CHOP combination followed by two-year maintenance with R. Although results of randomized trials confirmed that this approach results in an improved patients' outcome and made a step forward in the management of patients with FL, one important question that can be raised is if this approach is really needed for all patients with FL or if some of them could benefit from a reduced intensity treatment achieving the same results in terms of outcome and survival . This question is of particular interest for newly diagnosed patients for whom maintenance does not affect OS.   More recent data demonstrated that the outcome of patients with FL can be further predicted by evaluating the quality of response to therapy studying minimal residual disease (MRD). This project addresses the objective of evaluating if combining clinical response assessed on FDG-PET scan and molecular response measured through MRD detection could permit to single out groups of patients at different risk of progression and to consequently modulate maintenance therapies, with the aim to provide clinicians a more rational use of the available diagnostic and therapeutic resources."
 
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Comments on chemo PAL
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PAL update:
Red flags and free speech - tips on identifying implausible claims about cures for cancer   | PDF version
 
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Testing Lirilumab With Rituximab for Relapsed, Refractory or High-risk Untreated Chronic Lymphocytic Leukemia (CLL) http://1.usa.gov/1Djdng9

Search of: Lirilumab | lymphoma OR CLL - List Results - ClinicalTrials.gov http://1.usa.gov/1LcQMtK

Poster: Phase 1 dose-escalation study of lirilumab (IPH2102, BMS-986015, LIRI),
a fully human anti-KIR monoclonal antibody in patients with various hematologic (HEM) or solid (SOL) malignancies
http://bit.ly/1TFc9Fl

"The blockade of KIR by LIRI fosters the activation of NK cells, selectively enhancing the cytotoxicity of NK cells against tumor cells without affecting healthy tissues."
 
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Updated: Considerations at relapse of indolent lymphoma
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Patient-reported outcomes (PRO) in| lymphoma studies - ClinicalTrials.gov http://1.usa.gov/1QZgCEX
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Patient-reported outcomes (PRO) in cancer - ClinicalTrials.gov http://1.usa.gov/1dsBRfU
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Early-Stage Nodular Lymphocyte-Predominant Hodgkin Lymphoma: The Impact of Radiotherapy on Overall Survival. http://1.usa.gov/1RHhCJ0
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Belinostat for Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF Study http://bit.ly/1Ikqsf6
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Skeptical Raptor 2015:
Marijuana and cancer – what are facts and what’s just smoke  http://bit.ly/1e80VcE

Smoke ... I mean the assertion is just smoke.
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A Surprising Match: Cancer Immunotherapy and Mismatch Repair | NIH Director's Blog http://1.usa.gov/1BH8mCG

snip: ... it supports the hypothesis that immunotherapy may be most effective against tumors with many mutations. (In the new study, the tumor cells deficient in mismatch repair contained more than 20 times as many mutations, on average, than tumor cells proficient in mismatch repair.) The idea is that the greater the number of DNA glitches in a tumor cell, the more abnormal proteins it will produce—and the more abnormal proteins that are generated, the greater the odds that the body’s immune cells will regard the tumor cells as “foreign” and target them for destruction.
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PAL study of interest:

Testing engineered t-cells (CART19 /KTE-C19) in chemo-refractory Aggressive Lymphoma (NHL) – including transformed FL - ClinicalTrials.gov http://1.usa.gov/1HWFk4v  
Related report: *OncLive 2015:
AR-Modified T-Cell Therapy Shows Durable Response in Non-Hodgkin Lymphoma http://bit.ly/1QJGDbf
 
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PAL study of interest:

Relapsed aggressive lymphoma: KPT-330 + RICE for Relapsed/Refractory Aggressive B-Cell #Lymphoma, including transformed FL http://1.usa.gov/1HMlyqV

Technical Background on KPT-330 and related agents: Selective inhibitors of nuclear export for the treatment of non-Hodgkin’s lymphomas
http://1.usa.gov/1lVKX7u

Tumor suppressor genes are genes that begin the cell death process when defects develop in a cell ... to protect against cancer. The tumor suppressor genes are de-activated in cancer cells ... allowing the cells to persist and to be resistant to cancer drugs. Drugs that activate tumor suppressor genes have the potential to overcome drug resistance.
 
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Trial Talk ... experts you can consult for second opinions and also ask about clinical trials
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Highlighting Agents that Target Disease Pathways
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Dose - the importance of getting it right
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DLBCL page
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T-cell page
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Hodgkins Lymphoma page
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Medscape 2015:
For Refractory CLL, Venetoclax's (ABT 199) CR rate Is Tops http://wb.md/1BiYM8M 

snip: Dr Barr said, again, that this degree of MRD negativity is "unparalleled." Six patients were able to interrupt venetoclax after achieving a complete response or CRi, and while all six remained free of recurrence after a median time of 12 months (0-21) off the therapy, one MRD-positive patient had asymptomatic progression at 23.7 months after stopping therapy.

PAL query to find ABT 199 trials: http://1.usa.gov/SRZotl
 
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Polatuzumab Vedotin (PoV) is an antibody that binds to cd79b that delivers a drug payload.

* ASCO 2015: Durable responses: polatuzumab vedotin (CD79b antibody-drug conjugate) in relapsed/refractory follicular lymphoma http://bit.ly/1K6TuPM 

* PAL query for Polatuzumab Vedotin (PoV)
For trials see: http://1.usa.gov/1sd80LK 
 
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DLBCL Study of interest:  Rituximab and Combination Chemotherapy With or Without Lenalidomide for Newly Diagnosed Stage II-IV DLBC Lymphoma http://1.usa.gov/1BKHM6a
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Costs page

New Push Ties Cost of Drugs to How Well They Work - WSJ http://on.wsj.com/1GEYvhm  Your thoughts?

Comment:  What is worse than getting no treatment effect, lots of side effects, and having to sell your house to pay for it?

Pay for performance is an interesting idea. Among the deviling details would be how to define performance and if it can/should be based on individual vs. aggregate outcomes? Not to mention how you attribute good or bad performance to parts of combination therapy? It seems doable, however … that prices for drugs on patent can be scaled in some ways to make the system fair to patients and sustainable for the healthcare system – without trashing incentives to develop and test new drugs.

A performance-based system, might help to focus research on achieving bigger clinically meaningful gains and on identifying and validating predictive biomarkers – to limit unproductive toxicities – physical and financial.  KarlS

 
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Medicare Plan Finder
for Health, Prescription Drug and Medigap plans http://1.usa.gov/1Eo9LbH 
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Medicare & You | Medicare.gov http://1.usa.gov/1IPWPTV
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CLL - Weill Cornell 2015:
FDA Grants Breakthrough Therapy Designation to Venetoclax (ABT-199)
for Patients with Relapsed/Refractory CLL with 17P Deletion http://bit.ly/1cmRGoX
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* The ASCO Post:
Researchers Discuss Pilot Study on Hallucinogenic Therapies for Cancer Anxiety http://bit.ly/1J7nTwN 

* PAL recommended - Medpage Today 2015:
Follicular Lymphoma: Watch/Wait Appropriate but Not Simple: Many patients can safely delay treatment, some cannot or maybe should not. http://bit.ly/1H52pBk

* Medpage Today 2015:
Expanding Options for Follicular Lymphoma Patients in Relapse; Studies of the microenvironment and immune system spark enthusiasm. http://bit.ly/1Eln0v5

*OncLive 2015:
Improving Outcomes in Mantle Cell Lymphoma http://bit.ly/1IsPAPO

* Science Daily 2015:
New treatment option for subtype of aggressive lymphoma ALCL http://bit.ly/1RwMwGC

* Eureka 2015:
'Dr. Google' doesn't know best -- search engine self-diagnosis and 'cyberchondria' http://bit.ly/1IO0sIP

* Medpage Today 2015:
Follicular Lymphoma: Watch/Wait Appropriate but Not Simple: Many patients can safely delay treatment, some cannot or maybe should not. http://bit.ly/1H52pBk

 
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This looks to be a registration trial based on the size (n=400) and that it's a controlled study with standard rituxan as the reference group. Registration studies are of particular importance to us patients and caregivers because they can be the basis for changing practice if the study is positive.

Testing IPI-145 (Duvelisib) With Rituximab vs Rituximab in Previously Treated Follicular Lymphoma - ClinicalTrials.gov http://1.usa.gov/1niDlai

Here's a technical article on the signaling target of this agent.
DEVELOPMENT OF DRUGS TARGETING THE PI3K SIGNALLING PATHWAY IN LEUKAEMIAS AND LYMPHOMAS http://bit.ly/1QqrurX


snip: "The PI3K family of signalling enzymes play a key role in the transduction of signals from activated cell surface receptors controlling cell growth and proliferation, survival, metabolism, and migration.

The intracellular signalling pathway from activated receptors to PI3K and its downstream targets v-akt murine thymoma viral oncogene homolog (Akt) and mechanistic target of rapamycin (mTOR) is very frequently deregulated by genetic and epigenetic mechanisms in human cancer, including leukaemia and lymphoma."
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Daratumumab
(immune-modulating antibody - targeting cell surface receptor cd38)

A fully human monoclonal antibody directed against the cell surface glycoprotein CD-38 with potential antineoplastic activity. The binding of daratumumab to natural killer (NK) cells mimics the normal CD38-CD31 interaction on the NK cell surface.

CD38 is also present on multiple myeloma (MM) cells and plasma leukemia cells; this agent may preferentially bind these cells, triggering antitumoral antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). CD38, a cell surface glycoprotein, is present on various immune cells and has been shown to regulate the cytotoxic response of activated NK cells.

Preclinical report: Daratumumab, a Novel Human Anti-CD38 Monoclonal Antibody for the Treatment of CLL and B-Cell Non–Hodgkin Lymphoma http://bit.ly/1coqc22 

Testing Daratumumab in Relapsed/Refractory b-cell lymphoma - ClinicalTrials.gov http://1.usa.gov/1EviaPN 

Search of: lymphoma OR CLL | Daratumumab - List Results - ClinicalTrials.gov http://1.usa.gov/1Js2nRj
 
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Testing Mocetinostat (HDAC inhib) w Brentuximab Vedotin in Patients With Relapsed or Refractory #Hodgkin #Lymphoma http://1.usa.gov/1Q6Wf4W 

mocetinostat
A rationally designed, orally available, Class 1-selective, small molecule, 2-aminobenzamide HDAC inhibitor with potential antineoplastic activity. Mocetinostat binds to and inhibits Class 1 isoforms of HDAC, specifically HDAC 1, 2 and 3, which may result in epigenetic changes in tumor cells and so tumor cell death; although the exact mechanism has yet to be defined, tumor cell death may occur through the induction of apoptosis, differentiation, cell cycle arrest, inhibition of DNA repair, upregulation of tumor suppressors, down regulation of growth factors, oxidative stress, and autophagy, among others. Overexpression of Class I HDACs 1, 2 and 3 has been found in many tumors and has been correlated with a poor prognosis.

NCI Drug dictionary - cancer.gov 
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PubMed
Disease characteristics, treatment patterns, prognosis, outcomes and lymphoma-related mortality in elderly follicular lymphoma in US http://1.usa.gov/1DOWg5T

Data from the National LymphoCare Study (a prospective, multicentre registry that enrolled follicular lymphoma (FL) patients from 2004 to 2007) were used to determine disease characteristics, treatment patterns, outcomes and prognosis for elderly FL (eFL) patients. Of 2650 FL patients, 209 (8%) were aged >80 years; these eFL patients more commonly had grade 3 disease, less frequently received chemoimmunotherapy and anthracyclines, ....

 
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Frontline rituximab monotherapy induction versus a watch and wait approach for asymptomatic advanced-stage follicular lymphoma: A cost-effectiveness analysis - Prica - 2015 - Cancer - Wiley Online Library http://bit.ly/1IrU3Th

Comment: from the summation and abstract it's not possible to judge the quality of the study methods. One would hope that the abstract would mention the number of patients studied ... to at least begin to estimate the significance of the findings. It seems counter-intuitive that a cost finding could be made ahead of a survival finding (for w&w vs. Rituxan when there is no need to treat.) Another consideration is if those on w&w will necessarily need a chemo-based therapy when treatment is needed. Also important to know is if the sponsor of R sponsored the study.

So I would not take this report as direct or indirect evidence of a practice-changing finding without having much more information. Perhaps expert commentary based on the full text of the report will follow and assist.  (KarlS)

 
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PAL subtopic: Epigenetics and diet as treatment for cancer?
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New topic: Hepatitis C and lymphoma
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2011 - full text:
Hepatitis C virus-related B cell subtypes in non Hodgkin's lymphoma http://1.usa.gov/1Givglc
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2015 - abstract:
Antiviral therapy: better survival in patients with hepatitis C virus and B-cell non-Hodgkin lymphomas, http://1.usa.gov/1J6fzOO
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Lancet 2015:
Carcinogenicity of tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate http://bit.ly/1HrIt9W
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WALDENSTROM'S

*Medscape 2015:
'New Era' in the Treatment of Rare Lymphoma http://bit.ly/1FnZGN6

*Dana Farber 2015:
New Waldenstrom's drug shows sustained benefit at two years http://bit.ly/1Og9HCz
 
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Vitamin D — Health Professional Fact Sheet https://bitly.com/1xRsO1D
 
Information for health professionals about Vitamin D, recommended intakes, sources, intake status, risks of inadequacy or excess, current research on Vitamin...
 
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DAJHO 2015
Clinical Applications and Limitations of Next-Generation Sequencing http://bit.ly/19RAl5n
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JAMA 2015:
Potential chemoresistance after consuming fatty acid in fish, fish oil  
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Find a Doctor, Specialist oncologist,
Dentist or Hospital Reviews, UCompareHealthCare http://bit.ly/1MbxVjZ
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PAL update:
Risk factors for lymphoma - autoimmune
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Jennifer R. Brown, MD, PhD
How I Manage Deletion 17p Chronic Lymphocytic Leukemia http://bit.ly/1MLTnZE

An important article (often technical) on a validated risk factor for high risk CLL . It includes her recommendations for treatment and how this has changed for this high risk group.
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Safety and efficacy of temsirolimus with Bendamustine in relapsed MCL and Follicular lymphoma - PubMed - NCBI http://1.usa.gov/19IQJpA

Snip:  An objective response was observed in 14/15 patients (93%), including 5 CR (33% all MCL). After a median follow-up of 19 months, 67% of patients are without signs of progression. Temsirolimus can be safely added to BR with promising preliminary activity.

temsirolimus (NCI Dictionary)
An ester analog of rapamycin. Temsirolimus binds to and inhibits the mammalian target of rapamycin (mTOR), resulting in decreased expression of mRNAs necessary for cell cycle progression and arresting cells in the G1 phase of the cell cycle. mTOR is a serine/threonine kinase which plays a role in the PI3K/AKT pathway that is upregulated in some tumors.   cancer.gov

 
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Blood 2015: Casulo, Burack, Friedberg
Transformed follicular non-Hodgkin lymphoma

HT (Histologic Transformed FL) is an important cause of morbidity and mortality in patients with FL. Given the biological heterogeneity of HT, and the relative rarity of the event, it is unlikely we will have prospective, randomized trials to guide management of this complication. However, anticipating rapid translation of genomic insights into clinical practice, the implementation of targeted DNA sequencing approaches, and a plethora of novel, targeted therapeutic agents in development, we look forward to a day soon when a molecularly defined, precision therapy approach will replace our current empiricism in the approach to HT.
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An easy way to weigh in from GovTrack.us:
H.R. 460 (113th): Patients’ Access to Treatments Act of 2013” http://bit.ly/1LeTZcW

Text of H.R. 460: Patients’ Access to Treatments Act of 2013 -  http://bit.ly/1x6bLsB

Key snip: A [plan] that provides coverage for prescription drugs and uses a formulary or other tiered cost-sharing structure shall not impose cost-sharing requirements applicable to prescription drugs in a specialty drug tier that exceed the dollar amount (or its equivalent) of cost-sharing requirements applicable to prescription drugs in a non-preferred brand drug tier (or prescription drugs in a brand drug tier if there is no non-preferred brand drug tier).
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study drug: copanlisib

Copanlisib inhibits the activation of a signaling pathway, which may result in inhibition of tumor cell growth and tumor cell survival NCI

Testing Copanlisib (PI3Kα/β inhibitor) and Rituxan
in Relapsed Indolent B-cell NH Lymphoma (iNHL) - ClinicalTrials.gov http://1.usa.gov/1Ca0eKE
 
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PAL update:
Agents that target disease pathways:  Terminology
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PubMed:
Geographic clustering for cutaneous t-cell lymphoma - PubMed - NCBI http://1.usa.gov/1F0MFMT
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Medscape 2015: (free registration / login required)
Does This Cause Cancer? http://bit.ly/1aLYxHk


Experts discuss evidence for and against BPA, Cell Phones, Artificial Sweeteners, Pesticides, Power Lines ... then give interesting verdicts

Comment: Environment exposures are typically associated with specific types of cancer. The strongest association is between cigarette smoking and lung cancer – which is striking and validated as a causal factor. Here the exposure to carcinogens in the smoke is at a very high level – often over long periods of time.   Unlike many other medical conditions, such as diabetes, limiting our exposure to what caused the condition will not help to reverse a malignant process once it has started – which, in short, is caused by genetic mutations causing the damaged cells to persist and grow abnormally.

… Giving up cigarettes or minimizing exposure to pesticides (good ideas for other reasons) will not undo the damage that was done to the genes in the malignant cells.

Why might this matter?  If I have it right, it means our focus can be on considering science-based approaches to treatment – that target what drives the underlying biology of the disease. (For lymphoma there are many!)  … We can otherwise live normal lives – taking part in a variety of wholesome foods and pleasures without worry about its effect on this medical condition.  KS
 
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MCL - biomarker for high risk:
miR-18b overexpression identifies mantle cell lymphoma patients w poor outcome and improves the MIPI-B prognosticator http://1.usa.gov/1EGKa21
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Welcoming Dr. Michael Bishop as a new scientific advisor to PAL

Thank you Dr. Bishop!
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ASCO Post:
Inotuzumab Ozogamicin (drug-antibody conjugate) Plus Low-Intensity Chemo:
A Winner in Older Patients With Leukemia http://bit.ly/1wnZIGP

PAL query:
inotuzumab ozogamicin trials for lymphoma http://bit.ly/8Bzg5Z

Measuring our impact and interest in this agent:
so far there have been 216 clicks on this query. See https://bitly.com/8Bzg5Z+ )
 
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The ASCO Post, 2015:
Radiotherapy in Good prognosis DLBC Lymphoma? http://bit.ly/1A6adZZ

“In this prospective study, the results demonstrate that in nonbulky limited-stage DLBCL, R-CHOP alone for 4 to 6 cycles induces very high complete response rates, with a very good overall survival and a very low relapse rate,”
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Dr Sharman's Blog 2015;
Syk not Sick http://bit.ly/1z5fvVz 

Dr Sharman discusses yet another pathway targeting drug: "Entospletinib looks to have pretty good efficacy in CLL. It is a twice daily pill. You really cannot compare across studies, but some of the early numbers look a lot like idelalisib. Lots of work left to be done and the trial is still recruiting patients with CLL (trial link here). Talk to your own doctor or seek an opinion at one of the centers offering the trial."

Entospletinib studies in lymphoma or CLL - ClinicalTrials.gov http://1.usa.gov/1ENLgqR 
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The Washington Post
Scientists just made the first map of the human epigenome.  http://wapo.st/17joH2e

See also background on
epigenome http://www.genome.gov/27532724 

Each person's body contains trillions of cells, all of which have essentially the same genome. Yet some cells are optimized for use in muscles, others for bones, the brain, the stomach and the rest of your body. What makes these cells different?

The protein-coding parts of your genome, called genes, do not make proteins all of the time in all of your cells. Instead, different sets of genes are turned on or off in various kinds of cells at different points in time. Differences in the types and amounts of proteins produced determine how cells look, grow and act. The epigenome influences which genes are active - and which proteins are produced - in a particular cell.

PAL topic updates: Epigenetics and HDAC inhibitors
 
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Low-dose pre-phase before conventional-dose chemotherapy for ulcerative gastric diffuse large B-cell lymphoma http://1.usa.gov/1DiNRMf
 
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Cancer. 2015 :  Elderly patients
Disease characteristics, patterns of care, and survival in very elderly patients with DLB-cell lymphoma http://1.usa.gov/1vQwPms 

Abstract conclusion statement: Although patients with DLBCL who were aged >80 years were less likely to receive R-CHOP, this regimen conferred the longest survival and should be considered for this population. Further studies are needed to characterize the impact of treatment of DLBCL on quality of life among patients in this age group.
 
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2015 Recommended Immunizations for Adults:
By Age and By Health Condition  CDC .gov PDF  http://1.usa.gov/19kzESt

Handy, two-page printable tables. 
 
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Measles and Measles Vaccine:
National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention 03/12 http://1.usa.gov/1BfMY6h 

Comprehensive overview and key facts … such as attenuated versus live versions of vaccines.
Live vaccines may be contraindicated in lymphoma and CLL patients.
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10 Ways Doctors and Patients Can Avoid Hating Each Other | Cancer Network http://bit.ly/1CsaVoF
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Being Mortal | FRONTLINE | PBS http://to.pbs.org/1CiCtNg

 ... Many positive comments coming in on this
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PAL update:
Agents that target disease pathways  (a printable brochure)
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Cell Death & Disease:
Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing http://bit.ly/1E4sTNU

Early but very interesting.  Not yet known if these potent agents can be given safely at therapeutic doses.

See also for background on
Dose - the importance of getting it right
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Being Mortal | FRONTLINE | PBS http://to.pbs.org/1CiCtNg

Many positive comments coming in on this
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PR release 2015:
Genentech (RHHBY) Shows Off Positive Phase III Lymphoma Data From Late-Stage Study http://bit.ly/1F6QJJO

GADOLIN (NCT01059630; GA04753g) is a Phase III open-label, multicenter, randomized two-arm study evaluating Gazyva plus bendamustine followed by Gazyva alone for up to two years compared to bendamustine alone in 413 patients with indolent non-Hodgkin’s lymphoma whose disease progressed during or following Rituxan-based therapy. The primary endpoint of the study is PFS, with secondary endpoints including response rate (RR), best response and overall survival (OS).

Comment:  Well I see to be eligible you had to be found refractory to Rituxan.
https://clinicaltrials.gov/ct2/show/NCT01059630  "Refractory to any previous regimen containing rituximab"

It will be interesting to see how many participants were deemed refractory to Rituxan based on the use of Rituxan as a single agent.
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Clin Cancer Res. 2015 Jan 28. pii: clincanres.2221.2014.

Combination of lenalidomide and rituximab overcomes rituximab-resistance in patients with indolent B-cell and mantle cell lymphomas. http://1.usa.gov/1ztj507

Comments: Interesting and encouraging ... but there are reasons to be cautious about basing conclusions (made by study authors in the title) on this or any single center, single-arm study. Notably it was open only to Rituxan-resistant indolent b-cell lymphoma and MCL. Without a control group it' not known how continued Lenalidomide without Rituxan would have compared to the study combination of continuous Lenalidomide given with standard Rituxan x 4. The study protocol describes also the use of low dos Dexamethasone .. oddly, not described in the abstract. https://clinicaltrials.gov/ct2/show/NCT00783367
 
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Study drug of interest:
Testing Procaspase Activating Compound-1 (PAC-1) in Advanced Malignancies - lymphoma -- ClinicalTrials.gov http://1.usa.gov/1zXsWvV

* Cell Death Dis. 2013 Dec; 4(12): e968.
Procaspase-activating compound-1 (PAC-1) a direct caspase-activating compound” http://1.usa.gov/1zp1pTi 

SNIP:  Procaspase-activating compound-1 (PAC-1) is the first small compound reported to convert procaspase-3 to active caspase-3, in vitro, by chelating inhibitory zinc ions from procaspase-3, thereby inducing effective cell death in tumor cells as well as mouse xenograft models.8, 9 This compound recently received increased attention because of its selective activity on cancer cells and promising antitumor activity in the canine lymphoma model.

Comment:  Very early (its' not known yet if the drug can be given safely at the active dose) but it's very interesting and potentially groundbreaking because it would be a new class of drug targeting a key pathway involved in treatment resistance.
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Youtube 2015:
Experts discuss Initiation and Discontinuation of Ibrutinib From   
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Onclive 2015;
FDA Expands Approval of Ibrutinib to Waldenström’s Macroglobulinemia  http://bit.ly/1zbBezU
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Notes on the importance of the dose  PAL
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Science Daily 2015:
Added benefit of idelalisib is not proven http://bit.ly/1AvcxNq

Snip:  The Federal Joint Committee (G-BA) specified "best supportive care" (BSC) as appropriate comparator therapy for the assessment of idelalisib in patients with refractory follicular lymphoma. BSC means a therapy that provides the patient with the best possible, individually optimized, supportive treatment to alleviate symptoms and improve quality of life.
 
See PAL's topic page on idelalisib  -
providing background on the accelerated approval of this agent by FDA PAL
 
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Login Req: Dunleavy, Wilson on
Molecular Subtypes of Diffuse Large B-Cell Lymphoma | Cancer Network http://bit.ly/1zIfRSE
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PAL Updates to Guidelines at Diagnosis:
 The biopsy and the Pathology Report
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A study of interest:
Rituximab With or Without Zevalin in Treating Patients With Untreated, Asymptomatic Follicular Lymphoma http://1.usa.gov/1xhtOvA 

One of the comparisons we proposed in the draft survey. What is missing is a w&w control arm, which is a competing standard for untreated, asymptomatic FL. Similarly, the study uses GELF to determine eligibility (no need to treat) with a minimum tumor size of 1.5 cm. It does not include rigorous molecular analysis, which could be especially informative if compared to tumors in an untreated control group.

Strengths include the random allocation, and the good sample size ... and that it compares immunotherapy to immunotherapy (minus immune suppressing chemotherapy pretreatment). I don't expect that QOL will vary significantly. Time to any treatment and Time to Chemotherapy are "soft" longer-term endpoints of interest. By "soft" I mean difficult to interpret because such decisions will be based on physician and patient opinion and not on objective predefined measures.

It will be interesting to see if this study accrues patients - given that either approach can be used off-study. So the key to accrual will be if there is there is genuine uncertainty about the benefit/risk comparison. Patients or physicians with a strong preference for either will do so off study. Here the risks of Zevalin may be perceived as being higher than for Rituxan - especially in the long term. This might be mitigated by a better anticipated CR rate and durations of remissions for Zevalin (the hypothesis) and that the safety of RIT is better (as for other treatments) in treatment-naive patients.

 
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Frontline Brentuximab vedotin in patients with CD30+ peripheral T-cell lymphomas: results of a phase I study. http://1.usa.gov/16DhbPz
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Autologous stem cell transplantation with in vivo purged progenitor cells in relapsed follicular lymphoma, abstract http://1.usa.gov/1GF2pob

After a median f-up of 6.7 years (range 1.5-13.6), 53% are still in CR. These data show that prolonged PFS is achievable in relapsed/refractory patients with high dose autologous transplantation of in vivo purged progenitor cells.

On this: "Preliminary studies using rituximab as in vivo purging during mobilization were effective in collecting lymphoma-free progenitor cells [11–16]. It has also been shown that the efficiency of harvested peripheral blood stem cell (PBSC) is not adversely affected by rituximab, and that engraftment and hematopoietic recovery are not compromised [17, 18].

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Immunochemotherapy with in vivo purging and autoSCT induces long clinical & molecular remission follicular lymphoma http://bit.ly/13nsnxB
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PAL update:
Questions for your doctor
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Drug-resistant follicular lymphoma cancer stem cells interacts with follicular dendritic cells http://1.usa.gov/1zAB8RG 

snip: In summary, we identified a novel CSC (cancer stem cell) population in FL and its signalling mechanism of interaction with the niche cells. Current treatments for FL are not curative for the majority of patients and were designed and deemed successful based on the response of the bulk population of tumour cells (Reya, et al 2001). Effects on a rare CSC population or on cells in the supportive microenvironment are unknown but presumed to be inadequate given the rates of relapse in FL. Understanding the essential signals for tumour chemoresistance and survival produced by FDC in FL may help develop novel therapeutic strategies (Burger, et al 2009). FL-SC biomarkers may also serve as prognostic markers to classify patients at higher risk of transformation or suggest alternative treatments.

The overall limitation of the current study is the considerable reliance on cell line-based studies with confirmation of the results using patient specimens. Given the limited availability of clinical specimens and the rare CSC population, it is a reasonable strategy to use a cell line model for exploratory experiments but requiring confirmation in clinical specimens. In future studies of FL, a much larger effort would be required to perform lymph node biopsies rather than fine needle aspirations in FL patients in order to collect a larger number of cancer cells to perform FL-SC studies. We believe that our studies, which identify and characterize the FL-SC and its interactions with the tumour microenvironment, are an important step in the development of biologically-based, curative treatments for FL.
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Medscape 2014 with video and text:
Double-Hit Lymphomas Explained, With Surprising EPOCH-R Data http://bit.ly/137qRzI


Cheson and Zelenetz on surprising reports at ASH
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TCGA Updates ‏@TCGAupdates
Insights into cancer biology through next-generation sequencing by Dr S Nik Zainal http://ow.ly/FBCNv 
 
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Consumer Reports News
Why is the health insurance Out-of-Pocket Maximum such a big deal? -  http://bit.ly/1GylTsI 

Especially important to consider for anyone with a chronic medical condition!
 
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Blood 2014: Transformed follicular non Hodgkin lymphoma http://bit.ly/1Gwptn4

Technical in large sections, but also contains therapeutic approaches of importance to patients - and encouraging news on improved outcomes in the Rituxan era.
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Science Based Medicine 2014:
Risks of CAM Treatments for Cancer http://bit.ly/1DaAsGx 
 
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Lymphoma SEER Statistics 1975-2011
5-Year Relative Survival (Percent)  by Age at Diagnosis 2004-2010 SEER
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Lymphoma Statistics - Rate, Count, and Annual Percentage Change - by subtype
Prepared by PAL from SEER database 2014  PDF

Surprising/alarming rise in Mediastinal large B-cell lymphoma
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Event-Free Survival at 12 Months (EFS12) from Diagnosis Is a Robust Endpoint for Disease-Related Survival in Patients with Follicular Lymphoma in the Immunochemotherapy Era 

Important milestone at 12 months helps to predict favorable outcomes.
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Patient to patient guidance from CT (wise words):
About finding, evaluating, choosing clinical trials About finding, evaluating, choosing clinical trials
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Updated December 2014:
"Giving" Tissue and Blood for Research - an advocate's perspective Giving-blood-and-tissue-2014.pdf
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New Research in Follicular Lymphoma http://bit.ly/1BtrUsA 

Dr. Wilson on the importance of new classes of agent (such as targeting b-cell signaling ... with comment on how we appear to be curing FL in some cases ... without using the C word.
 
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Added to PAL's trials of interest
Selinexor and Ibrutinib in Treating Patients With relapsed or refractory CLL or Aggressive Non Hodgkins Lymphoma - ClinicalTrials.gov http://1.usa.gov/1AvkvFV

Selinexor (KPT-330) lymphoma trial query - ClinicalTrials.gov http://1.usa.gov/1xs0cJv
Report ASH 2014: The Oral Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) Demonstrates Broad and Durable Clinical Activity in Relapsed / Refractory Non Hodgkin’s Lymphoma (NHL)

 
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Blinatumomab wins accelerated approval for Ph-negative relapsed or refractory ALL - 12/3/14 http://ln.is/ow.ly/d6XpY 

Comment: This agent targets cd19 and therefore might be used off-label for b-cell lymphoma in cases where there are no effective options (noting that biTE also has significant risks). The accelerated approval (based on a single-arm study) could also spur additional study in high-risk NHL. A report I've copied further below describes clinical experience in other b-cell malignancies. 

The approval was based on the achievement of durable complete remission (CR) and response with a reduction in minimal residual disease (MRD) to less than 10-4 in a multicenter single-arm trial (Protocol MT103-211) that enrolled 185 patients with R/R ALL. Blinatumomab was administered by continuous infusion for 4 weeks of a 6-week cycle. Up to two cycles were used for induction and three cycles for consolidation.



Paper on this agent: Unleashing the clinical power of T cells: CD19/CD3 Bispecific T cell engager (BiTE®)
antibody Blinatumomab as a potential therapy http://bit.ly/1yUZPYo 

Clinical responses were seen at doses of 15 μg/m2/day and higher. At 60 μg/m2/day, the overall response rate (ORR) was 75% across indolent lymphoma subtypes (18 out of 24 patients) with the highest response rate in follicular lymphoma (80%). Additionally, clearance of tumor infiltrate in the bone marrow was seen in 5 out of 6 patients with bone marrow involvement. No objective responses were seen below the 15 μg/m2/day dose (27).
 
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Biomarker update:
Elevated serum levels of IL-2R, IL-1RA and CXCL9 are associated with poor survival in follicular lymphoma http://1.usa.gov/1v6K8wt
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ASH: R-Benda Vs R-CHOP As Initial Treatment for Advanced Stage Low Grade Follicular Lymphoma:
A Matched-Pair Analysis http://bit.ly/1y3JPTT

An interesting approach to comparing outcomes in different studies - showing differences in the populations receiving one or the the other treatments, such as differences in SUV or meeting GELF criteria for need to treat.
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ASH: T Cells Expressing CD19-Specific Chimeric Antigen Receptors Inhibited By
Indoleamine 2,3-Dioxygenase in Tumors http://bit.ly/1y3crwK


Targeting a mechanism of resistance to CART19
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Bexxar revisited - comments on it's discontinuation by GSK
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ASH 2014 oral session abstracts on follicular lymphoma  - compiled 
DLBCL oral sessions added today
Paper: Quality of Life at Diagnosis Independently Predicts Survival in Patients with Aggressive Lymphoma http://bit.ly/1qPcHZN
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PAL update:
Kidney toxicity - background on treatment related risks and how to manage  PAL
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NEJM ,
Changes in Medical Errors after Implementation of a Handoff Program — http://bit.ly/1sjdmTu

Preventable adverse events — injuries due to medical errors — are a major cause of death among Americans. Although some progress has been made in reducing certain types of adverse events,1-3 overall rates of errors remain extremely high.4 Failures of communication, including miscommunication during handoffs of patient care from one resident to another, are a leading cause of errors; such miscommunications contribute to two of every three “sentinel events,” the most serious events reported to the Joint Commission.5 The omission of critical information and the transfer of erroneous information during handoffs are common.6 As resident work hours have been reduced, handoffs between residents have increased in frequency.7
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PAL update to Compassionate Use:
FDA video explains Expanded Access to Investigational Agents (for patients not eligible for trials) PAL
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Testing Rituximab, Romidepsin, and Lenalidomide for Recurrent / Refractory B-cell Non-Hodgkin Lymphoma http://1.usa.gov/1rYbgaD

This dose-finding study will be open to all subtypes of relapsed or refractory b-cell lymphoma.    Lenalidomide is thought to enhance the activity Rituxan by modulating the immune system and by direct activity.   Romidepsin binds to and inhibits histone deacetylase (HDAC), resulting in alterations in gene expression and the induction of cell differentiation, cell cycle arrest, and apoptosis.   Romidepsin is FDA approved for the treatment of t-cell lymphoma.
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It's Flu season and Flu vaccination time
.. for info on this and other types of immunizations: Immunization Guide

Contrary to a urban and rural legends, taking vitamins will not protect you from a viral infection.  Instead, the key way to protect from these infections is to educate the immune system about viral antigens so if you are exposed to the real virus the immune system can quickly respond -- having already developed memory cells from exposure to the virus antigen in the vaccine.  Washing your hands before touching your eyes, nose or mouth can help too.
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The ASCO Post Brentuximab Vedotin Shows Antitumor Activity in Patients With Relapsed Peripheral T-Cell Lymphoma http://bit.ly/1G6asLx 

Among the 14 patients achieving an objective response, 8 had complete responses, including 5 patients with angioimmunoblastic T-cell lymphoma. At the time of the study report, the median duration of response for all patients was 7.6 months, with five responding patients remaining in follow-up and five on therapy.

This will lead to a study testing this agent as a part of first line therapy for this very challenging indication.

• PAL Query to help patients and physician locate such trials:

Studies for peripheral t-cell lymphoma testing Brentuximab Vedotin - List Results - ClinicalTrials.gov http://1.usa.gov/1DGscZU
 
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PAL update:
Observation-enriched Randomized Clinical Trial - at a glance

A graphical schema of a hybrid study design includes a concise outline of when it is needed and how to mitigate bias.
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PAL update:
Big Picture Questions - to help optimize treatment consults  PDF
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2014, Report on outcomes for auto or allo transplantation for transformed follicular lymphoma to DLBCL - NCBI http://1.usa.gov/1tkz4e6

We analyzed transplantation outcomes in 141 subjects with biopsy-proven diffuse large B-cell lymphoma transformed from follicular lymphoma reported to the Center for International Blood and Marrow Transplant Research between 1990 and 2009. Two groups were identified: autologous HCT (auto-HCT; n = 108) and allogeneic HCT (allo-HCT; n = 33). Fewer auto-HCTs were done for transformed follicular lymphoma in 2003 to 2009, with a shift favoring allo-HCT. ...
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Ofatumumab in Refractory Chronic Lymphocytic Leukemia: Experience ... - PubMed - NCBI http://1.usa.gov/1Dx2IxZ

results confirm the efficacy and acceptable tolerability profile of ofatumumab as a single agent in severely ill patients with CLL
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Testing APTO-253 HCl in Patients With Relapsed or Refractory Hematologic Malignancies http://1.usa.gov/1wFens8

Background from sponsor: http://aptose.com/apto-253/

APTO-253 is a novel small molecule with potent anti-tumor activity in cancer cells via tumor suppressor induction leading to cell cycle inhibition and programmed cell death. APTO-253 has been shown to induce the tumor suppressor gene Krüppel-like factor 4 (KLF4) and expression of p21, leading to cell cycle arrest and apoptosis. Nonclinical pharmacology studies have demonstrated that APTO-253 exerts in vivo anti-tumor activity in solid tumors and hematologic cancers. Aptose completed a Phase 1 study in patients with advanced or metastatic solid tumors in which promising clinical activity was observed.
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Testing PI3k Delta Inhibitor TGR-1202 + Ibrutinib in Patients With Select B-Cell lymphoma http://1.usa.gov/1zvYgmu

Technical background by the sponsor (for shareholders) on this agent ... that appears to be similar to IPI-145 with hopefully less liver toxicity: http://bit.ly/1wtng9h

"TGR-1202 has a different [chemical] backbone designed to potentially minimize liver toxicity while preserving delta specificity."  
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Lenalidomide + Rituximab THEN: Lenalidomide OR Rituxan Maintenance for Relapsed/Refractory FL, MCL, MZL Lymphoma http://1.usa.gov/1857Xen

* Discussion:  Dr Sharman 2014:
Lenalidomide and Rituximab in Lymphoma http://bit.ly/1DGFtTU
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Update to Agents Targeting Disease Pathways:
index of targeted agent in right column with links to trials and reports.
agents - background on novel classes of agents for lymphoma
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Support Patients Against Lymphoma:

Bid on Original Ink Drawing of Piglet by Artist US Small Matted Realism

eBay http://ebay.to/1CPDevg  Bid starting at $12.00
 
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ASCO: Cymbalta Tames Post-Chemo Pain http://bit.ly/1rpT0GO 
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Testing Ibrutinib (BTK Inhibitor) With Carfilzomib (Velcade-like) in Relapse/Refractory Mantle Cell Lymphoma http://1.usa.gov/ZEU5Ee 

Carfilzomib is the same class of agent as Velcade, which is approved for MCL. This is an interesting combination in that each agent works by a different, and potentially complementary, mechanism of action as described in the following technical paper.

* PubMed: Screening identifies synergistic co-targeting of Bruton's tyrosine kinase (ibrutinib) and the proteasome (Velcade/Carfilzomib) in mantle cell lymphoma http://1.usa.gov/1uAmwf0 
 
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For ways to help continue PAL into the future, please visit our page: How to Help http://bit.ly/7tqwqL
 
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Hematologica, Oct 2014:
Three major uncertainties in the antibody therapy of cancer http://1.usa.gov/1wkwnYK
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NEJM:
CART19 and B-cell aplasia - a surrogate for persistent engineered t-cells -- associated with response http://bit.ly/1wrjgHc

Normal and malignant b-cells are ablated by the engineered t-cells programmed to kill cells expressing cd19.
The persistence of CART19 cells (and activity against tumor cells) can be gauged by the persistence of b-cell depletion.
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PAL Perspective:
Quality of Life as an endpoint in clinical trials QOL
 
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Study of interest:
Testing Polatuzumab Vedotin With cd20 antibody With Bendamustine in Relapsed or Refractory Follicular DLBC Lymphoma http://1.usa.gov/1CgRltd

* About Pinatuzumab Vedotin Antibody-Drug Conjugate - BioOncology http://bit.ly/ZXRo1t

The expression of the CD22 receptor is limited to B cells and is present on non-Hodgkin’s lymphoma (NHL) cells and chronic lymphocytic leukemia (CLL) cells. Pinatuzumab Vedotin is an antibody-drug conjugate (ADC) composed of a monoclonal antibody (MAb), a stable linker, and the cytotoxic auristatin, and it is designed to selectively bind to CD22 while minimizing cytotoxic effects on hematologic cells that do not express CD22.

Comment: An interesting potential home run approach for patients with an unmet need (relapsed or refractory FL or DLBCL)
 
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Trial of interest:
Testing ACP-196 (Btk Inhibitor) for relapsed Novo Activated B-cell (ABC) Subtype of Diffuse Large B-Cell #Lymphoma http://1.usa.gov/1vQEUCH 

A trial of interest … perhaps when potentially curative high-dose therapy with stem cell rescue (transplant) is not an option or following second line transplant.

• More trials in other settings:

ACP-196 (btk-inhibitor) trials - List Results - ClinicalTrials.gov http://1.usa.gov/1yPA91J

NCI Drug Dictionary:

BTK inhibitor ACP-196

An orally available inhibitor of Bruton’s tyrosine kinase (BTK) with potential antineoplastic activity. Upon administration, ACP-196 inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways.

... This leads to an inhibition of the growth of malignant B cells that overexpress BTK. BTK, a member of the src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.


Comment: Informal reports by one investigator is that this agent appears to be very active and it has better safety than a well-known competing agent in this class.
 
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Testing Urelumab (IMID antibody) With Nivolumab (pd1 antibody) in Solid Tumors & B-cell Non-Hodgkins Lymphoma - http://1.usa.gov/ZwSKA7

Not yet recruiting. Recruiting sites (none yet posted) have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com

Urelumab (ue rel' ue mab; also known as BMS-663513 and anti-4-1BB antibody)

A humanized agonistic monoclonal antibody targeting the CD137 receptor with potential immunostimulatory and antineoplastic activities. Urelumab specifically binds to and activates CD137-expressing immune cells, stimulating an immune response, in particular a cytotoxic T cell response, against tumor cells. CD137 is a member of the tumor necrosis factor (TNF)/nerve growth factor (NGF) family of receptors and is expressed by activated T- and B-lymphocytes and monocytes; its ligand has been found to play an important role in the regulation of immune responses. Check for active clinical trials or closed clinical trials using this agent.


Nivolumab (nye vol' ue mab), nivolumab

A fully human monoclonal antibody directed against the negative immunoregulatory human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1/PCD-1) with immunopotentiation activity. Nivolumab binds to and blocks the activation of PD-1, an Ig superfamily transmembrane protein, by its ligands PD-L1 and PD-L2, resulting in the activation of T-cells and cell-mediated immune responses against tumor cells or pathogens.

Activated PD-1 negatively regulates T-cell activation and effector function through the suppression of P13k/Akt pathway activation.

 
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JCO:  Event-Free Survival at 24 Months: Is a Robust End Point (predicting survival) for Disease-Related Outcome in Diffuse Large B-Cell Lymphoma http://bit.ly/Z0qDZe
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Dr. Wyndham Wilson:
Watch and Wait or Continuous Therapy for Follicular Lymphoma: Where Are We Now? - YouTube http://bit.ly/1yyhmrq
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Dr. O'Conner: T-Cell Lymphoma Treatment and Research Update - YouTube http://bit.ly/1pCTs3Q
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PAL update:  Resource added
Cardiotoxicity and Cardiomyopathy - Managing Side Effects - Chemocare Side Effect - Cardiac
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Testing Lambrolizumab (PD1 antibody) in
Relapsed or Refractory Stage IIB-IVB Mycosis Fungoides or Sezary Syndrome - http://1.usa.gov/1Dxnpws
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PAL update:
A checklist for reporting pain to our doctors  PAL
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PAL update: 
We've received very positive expert comment ... and have taken advice to rename the proposal:
The Observation-enriched Randomized Controlled Trial
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Medscape (free login req.) ...
CAR T Cells: A Look Under the Hood and Down the Road http://bit.ly/1wFSHMW
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'Scary' Decline in Funding for Cancer Research http://bit.ly/1paBc2j
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PAL topic update -
vaccine for shingles?  Insights by Dr. Furman:  Vaccine for shingles?
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NOVA | Vaccines—Calling the Shots http://to.pbs.org/1Drlae0

Vital public education, well done, information and misinformation on vaccines, some kinds that prevent cancer.

Please share widely. Set aside time to watch with family and friends.
 
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Dr. Myron Czuczman:
Upbeat Perspective on Progress in Lymphoma | Lymphoma | Patient Power http://bit.ly/1wMWdI8
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ABC Radio National On-Demand Player:
A call for clinical cancer trials to be more efficient http://ab.co/1s5ar6f
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Technical:
Genetics of Follicular Lymphoma Transformation - supports divergent evolution from a common mutated precursor http://bit.ly/1tO4OWm  Full text PDF

The first finding of our study is that, although all FL-tFL sample pairs have a clear clonal relationship, the dominant tFL clone arises in most patients from a mutated CPC (common precursor cell) through the acquisition of independent genetic events, consistent with divergent evolution.

The existence of this CPC cannot be physically demonstrated, but it can be postulated on the basis of the presence of a set of lesions that are shared between FL and tFL, and is consistent with previous studies based on the analysis of the rearranged Ig genes (Carlotti et al., 2009) as well as with recent work on FL progression (Green et al., 2013).


Comment:  These finding may influence the approach to treating follicular lymphoma ... suggesting the need to target also the common precursor cell if treatment is to have a potential for cure.
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Blood, 2013, Technical:
Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma http://1.usa.gov/1i9QCQ4

To date, most mutations in NHL have been reported on a presence/absence basis with little attempt to evaluate their subclonal representation. We therefore aimed to investigate the degree of intratumoral genetic diversity within FL to evaluate the plausibility of gene mutation-directed therapies in this disease. We sorted tumor cell subpopulations based on their expression of CD20 and interrogated their mutational spectra using exome sequencing. This not only identified significant stratification of somatic mutations within tumor cell subpopulations within the same physical site, but also identified 2 contrasting patterns of disease relapse.
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Dr Sharman 2014:
Can CLL be cured? http://bit.ly/ZeEITc  posted to CLL topic page.

The point I wish to make is this.  The new drugs are very "sexy."  It is very appealing to think of  taking a non-chemo pill rather than chemotherapy, but if I am ever a patient with CLL and IgVH mutated BCR lacking 17P/11Q/TP53/NOTCH1/SF3B1 abnormality, I will absolutely take chemoimmunotherapy because there is a VERY GOOD chance I will not have to think about my CLL for many years, and based upon these two studies, I think he plateau in the survival curve is very provocative.   
 
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Lymphoma survivors are at a higher risk for this dangerous skin cancer.
The following compares normal to abnormal moles as you advance each slide.

The ABCDEs of Moles and Melanomas | Cancer Network http://bit.ly/1BuK0rz
 
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Lymphoma Awareness Month is September

Here is PAL's revised printable brochure to help raise awareness and understanding:  PDF
 
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J Clin Onc 2014:
CART19 in Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma and Indolent B-Cell Malignancies  http://bit.ly/Y5MbDV
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Cheson et. al: 
Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and NHL
The Lugano Classification http://bit.ly/1pwwzEF
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Testing Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies - PTCL only for expansion phase http://1.usa.gov/1vC5xv6

Based on encouraging unpublished anecdotal reports and lack of effective standard protocols in this setting.


Columbia University Medical Center Recruiting
New York, New York, United States, 10019
Contact: Ameet Narwal 212-326-5720 an2284@columbia.edu
Principal Investigator: Jennifer E Amengual, MD
 
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The Cancer HUman Biobank (caHUB)
Biospecimens.cancer.gov: http://1.usa.gov/1r2gfrQ 

Consensus of the Broad Scientific Community:
The lack of high-quality, clinically annotated human specimens has
become the limiting factor for translational cancer research.

Understanding the Problem:

The Siloed National Biobanking Landscape

• Collection, procession, storage procedures differ
• Degree and type of data annotation varies
• Scope and type of patient consent differs
• Access policies are lacking or unknown to potential users
• Materials transfer agreement conditions differ
• Supporting IT structures differ in capacity and functionality

→ WIDE VARIATION IN QUALITY OF SPECIMENS AND DATA

 

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An advocate's perspective : "Consent" for unspecified future use?
 

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PAL update: 
Giving Tissue and Blood
- an advocate's perspective PDF
 

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Important for advocates:
FDA Patient Representative Workshop - videos available for each session http://bit.ly/YXBAuS
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NCTN 2014 Working Group Report on Cooperative Group Trials  PDF

Must read for advocates and investigators
===

 

ASCO 2014 Lymphoma Abstracts  & CLL, MDS, transplant

* Recognizing and Reporting Misleading Medical Promotion  PAL

* PAL update: CT imaging page  PAL

Accredited Facility Search - American College of Radiology 
FDA resource on Computed Tomography (CT)
And a handy record to track your imaging history
* PAL topic: 
DLBCL - cell of origin ABC or GCB?   PAL
A reliable test for cell of origin in DLBCL appears to be on its way ... to guide participating in trials, not yet clinical practice.
* PAL topic:
Autophagy and lymphoma ... a promising treatment target? PAL
* Best Practice Res Clinical Haematol. 2011:
Host genetics in follicular lymphoma Posted to Risk factors

Given an estimated lifetime risk of NHL of 1 in 48 (2.1%) in the United States [1] and a RR of 1.5 for the risk of NHL in first degree family members [13], then the absolute lifetime risk of NHL is 3.2% in first degree relatives of an NHL patient.  ...
* PAL topic:
Routine CT surveillance for lymphoma?   Imaging and Tests
* PAL update: new agent of interest:

Testing ACP 196 (next gen BTK inhibitor) in Mantle Cell Lymphoma  http://1.usa.gov/1w6GhkC

Anticipated to have greater specificity for the BTK pathway and therefore less toxicity ... based on animal studies.

Canine study describes properties of ACP 196: vetcancertrials.org/
*  Study of Interest:
Testing IPI-145 With Rituximab vs Rituximab in Previously Treated Follicular Lymphoma -
Clinical Trials of Interest    (Not yet recruiting)
* Follicular, relapsed/refractory:
Testing Nivolumab (immune checkpoint blockade) in  Lymphoma Clinical Trials of Interest  

Locations:  Many, international Key eligibility:  > or = 2 prior treatment lines; each of the 2 prior treatment lines must include at least Rituximab and/or an Alkylating agent
PAL trial of interest:

* CLL, SLL untreated with need to treat Comparing Ibrutinib + Rituximab to FCR 
Clinical Trials of Interest   Locations:  Multi-center, international
* Relapsed/refractory CLL
Testing Lenalidomide, Rituximab and Ibrutinib
Clinical Trials of Interest  

Location: Georgetown Univ.

PAL updates
About Cancer, Agents that Target disease pathways.

For a cancer to develop, internal and external defenses against cancer are suppressed

.... Tumor suppressor genes are inactivated or mutated (first-line, internal defense against cancer)

Genes that protect the cell from becoming a cancer
(such as repair copy errors or induce cell death when damage is detected) are silenced.  
Reactivating these genes with targeted treatment is a promising approach to treating cancer.
(e.g., epigenetic agents that reactivate tumor suppressor genes)


Tumors suppress the immune system (second-line, external defense against cancer). 

Cancer fighting t-cells are put to sleep.
Targeting these factors can reactivate the immune system to fight the cancer
(e.g., antibodies that target immune checkpoint blockade)

Thanks to the time it takes to draw the chalkboard illustrations, the layperson can follow the excellent explanations of cancer mutations and the role of tumor suppressor genes that follow:

* Video - Andrew Wolf:  Mutations in cancer

* Video - Andrew Wolf:  On tumor suppressor genes 

 

* Technical background on biology of FL / Feb 2014
Integrated genomic analysis identifies recurrent mutations and evolution patterns driving follicular lymphoma
 Follicular B-cell lymphoma - New

* Study of Interest:
Testing Ibrutinib in Relapsed or Refractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma
 
Clinical Trials of Interest  

*Dr Sharman's Blog 2014:
Ibrutinib in 17P deleted
CLL Advocate's perspective on 

Comment: Here we see an exemplary example of a biomarker that spares patients from ineffective therapy! If you have CLL with the 17p deletion (a specific mutation) then chemo will not work for you. Better yet, patients with this mutation respond great to a much less toxic targeted drug. ...

* Mamessier et al,
Nature and importance of follicular lymphoma precursors
 Posted to Follicular B-cell lymphoma - in the news

Follicular lymphoma exemplifies this multistep pathway of oncogenesis (development of a tumor).  In recent years, variants of follicular lymphoma have been recognized that appear to represent clonal B-cell expansions at an early stage of follicular lymphoma lymphomagenesis (growth and development of lymphoma).
* The ASCO Post: FDA approves Idelalisib http://bit.ly/1nVQPc3

The U.S. Food and Drug Administration (FDA) today approved idelalisib (Zydelig) to treat patients with three types of blood cancers. The FDA has granted traditional approval to idelalisib in combination with rituximab for patients with relapsed chronic lymphocytic leukemia and accelerated approval for patients with relapsed follicular B-cell non-Hodgkin lymphoma and relapsed small lymphocytic lymphoma who have received at least two prior therapies.
* Comparing ABT-199 + Bendamustine + Rituximab (BR) to BR or ABT-199 + R
 in Relapsed Refractory Follicular Lymphoma - Posted to Clinical Trials of Interest  

* PAL update, side effects:
CTEP:  Possible side effects for commonly prescribed oncology drugs http://1.usa.gov/1k8El68

Posted to Side effects
* Testing Ibrutinib in Patients With Refractory Follicular Lymphoma - ClinicalTrials.gov http://1.usa.gov/1gxUHCB
Posted to Clinical Trials of Interest   Multiple sites
PAL Background: BtK  Inhibitors

Key eligibility: chemoimmunotherapy-resistant FL whose disease has relapsed from at least 2 prior lines of therapy, including at least 1 rituximab combination chemotherapy regimen. Each patient must have resistant disease to the last therapy (defined as progression of disease [PD] during or within 12 months of the last dose of chemotherapy in a CD20 antibody combination chemotherapy regimen.
* PAL update:
 Informed consent topic page:  PAL
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* Science-Based Medicine
Evaluating Treatment Claims: A Primer http://bit.ly/1zFcwXo

Comment: A must read for anyone who is an active partner in their healthcare.
* PAL update:
Ibrutinib studies for lymphoma only (excluding CLL)
http://1.usa.gov/U56u1f  added also to PAL's trials by by AGENT 

*Leuk Lymph 2014:
The comparison of GELOX (Gemcitabine, Oxaliplatin, and L-asparaginase) and EPOCH as First-Line Chemotherapy in Patients with Stage I E to II E Extranodal Natural Killer/T-Cell Lymphoma: a multi-center retrospective study. http://1.usa.gov/1zwfpty

Comment: Because of the rarity of this type of lymphoma, prospective studies are not feasible to get done. In this case the case for GELOX seems strong because of the good size and the significant improvement in the outcomes across treatment centers .. possibly overcoming the limitations of the retrospective design ...

* Leuk Lymph 2014:
Therapy with bortezomib plus lenalidomide for relapsed/refractory mantle cell lymphoma: Final results of a phase II trial (CALGB 50501). http://1.usa.gov/1oR3xgd

Comment: A so-called failed or negative study showing that combining active drug A with active drug B ... does not necessarily lead to synergy. The trend now is to combine agents based on complementary mechanisms of action. Here ... who can say, but perhaps bortezomib worked against (instead of enhanced) the immune modulating activity of Lenalidomide?
* An advocate's perspective on expensive on-patent treatments that can be given on a daily basis -- indefinitely as maintenance until progression

The wonderful news is that some of these new targeted drug products can save lives and reduce the suffering of patients.  However, our society has to find a way to ensure access to these drugs without bankrupting the patient ...  or the public who will see their insurance premiums and taxes rise as the number of such agents increases and their use becomes routine. 

The financial toxicity should be accounted for and mitigated.  The sponsor's payment programs to assist patients with copayments are helpful to the patients, but this assistance can contribute to setting exorbitant prices that must be paid out by insurance providers... putting our health care system and economy in jeopardy.

* NEJM - Perspective:
Drug Companies' Patient-Assistance Programs — Helping Patients or Profits?

Posted to PAL: Rising Costs and  Access to Quality Cancer Care  

* Leukemia 2014:
Cheson, Hiddemann - How we manage follicular lymphoma - Posted to Follicular B-cell lymphoma - In the News 

... the hope is justified that the long-term perspectives of patients suffering from the disease will be further improved in the near future.
* BIG News! 
Penn gets FDA 'breakthrough' designation for experimental cancer therapy
Posted to Reports  Programmed T-cells - Licensed to Kill (CAR T-cells)  
* Weil Cornell 2014:
FDA Announces Approval for Beleodaq (belinostat) in Treatment of Peripheral T-cell Lymphoma FDA Announces Approval for Beleodaq in Treatment of Peripheral T-cell Lymphoma http://bit.ly/1t6j54x 

“The safety and effectiveness of Beleodaq was evaluated in a clinical study involving 129 participants with relapsed or refractory PTCL. All participants were treated with Beleodaq until their disease progressed or side effects became unacceptable. Results showed 25.8 percent of participants had their cancer disappear (complete response) or shrink (partial response) after treatment.”


belinostat  A novel hydroxamic acid-type histone deacetylase (HDAC) inhibitor with antineoplastic activity. Belinostat targets HDAC enzymes, thereby inhibiting tumor cell proliferation, inducing apoptosis, promoting cellular differentiation, and inhibiting angiogenesis.

This agent may sensitize drug-resistant tumor cells to other antineoplastic agents, possibly through a mechanism involving the down-regulation of thymidylate synthase.
* PAL content: Overview of NCI Informed Consent
NCI-informed-Consent-template-At-glance.pdf
* PAL update to Trials of Interest
* CPI-613 + Bendamustine in Treating for Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma or Hodgkin Lymphoma
* PAL resource: Bone density -effect of lymphoma and treatment
Bone density loss related to  lymphoma and treatmetn
* PAL resource
added to Drug payment support
 
Medicare.gov: Pharmaceutical Assistance Program index of drugs with such programs http://1.usa.gov/1irc1L2 

Some pharmaceutical companies offer assistance programs for the drugs they manufacture. Click on the first letter of your drug name to see if any programs are available for the drugs you are taking. If your drug is on the list, click on "details" for detailed information about the program.
* PI3K Delta Inhibitor TGR-1202, in Combination With Brentuximab Vedotin for Hodgkin's Lymphoma Patients” http://1.usa.gov/1lBvVC8
Rationale: ASH Paper: - PI3K-δ Inhibitor TGR-1202 With Brentuximab Vedotin Synergistically Induces G2/M Phase Arrest and Cell Death In Hodgkin Cell Lines http://bit.ly/1qppOEu

 

June 16 - PAL updates

* PAL update:
About Our Trial Tools
* PAL's Picks - Studies of interest:
 PDF explains this tool
* PAL Update:  Find trials
by TYPE of LYMPHOMA AND Treatment Status  (updated counts and formats)
* PAL Update:
Clinical Trials: How to Ask about Trials
* PAL advocacy:
The ASCO Post: Omel, Schwartz
A Proposal for Patient-Selected Controlled Trials: Good Science and Good Medicine -http://bit.ly/1oXhCHR 


A hybrid controlled trial is proposed for circumstances where full enrollment is unlikely for a traditional randomized clinical trial. Here the patient is randomized to the study arm if he or she (or the treating physician) has no strong preference. Otherwise the choice of study arm is made by the patient and the risk factors in the study arms are balanced using various techniques-- such as propensity scoring.
NEWS HIGHLIGHTS:

* Brian Koffman's Blog 2014:
ASH 2013: Dr. Byrd Discusses Dinaciclib and the Need for More New Drugs to Treat CLL (chronic lymphocytic leukemia) http://bit.ly/1kSdqty

*Cancer Network 2014:
Post-Induction PET Predicts Survival in Follicular Lymphoma - http://bit.ly/1kUIdWx
* Molecular Analysis for Therapy Choice (NCI-MATCH) ...
coming soon: agents - background on novel classes of agents for lymphoma 

Eligible patients with solid tumors or lymphomas who do not have other standard treatment options will have DNA sequencing of their tumor limited to a specific panel of actionable mutations.  If one of these actionable mutations is found, the patient will be treated with a corresponding, targeted agent or combination of agents to determine if the tumor is responsive.

June 2

* Investigational PD-1 Immune Checkpoint Inhibitor Nivolumab Receives U.S. FDA Breakthrough Therapy Designation for Hodgkin Lymphoma | Antibodies | News Channels Posted to News- Immune Therapy  
* Comparing Idelalisib With Bendamustine and Rituximab (BR)
to BR for Previously Treated Indolent NHL
Posted to Clinical Trials of Interest  

Many US locations
* Medscape 2014, Dr. Cheson:
What to Watch in Lymphoma, Leukemia http://bit.ly/1ncH4tJ 

* Study of interest:
Expanded Access for Idelalisib in Combination With Rituximab in Chronic Lymphocytic Leukemia - ClinicalTrials.gov
Posted to Clinical Trials of Interest  

* ASCO 2014
Alliance: A phase II trial of lenalidomide plus rituximab in previously untreated follicular lymphoma.
Posted to Follicular B-cell lymphoma

* ASCO 2014:
Value of PET-CT after frontline therapy in follicular lymphoma: A pooled analysis
Posted to Follicular B-cell lymphoma
* Sonali Smith, 2013:
Dissecting follicular lymphoma: high versus low risk:
Posted to Follicular B-cell lymphoma  
* ASCO Post, 2014: Andrew D. Zelenetz, MD, PhD
Treating the Elderly Lymphoma Patient With Elevated Bilirubin”
Posted to NHL in elderly patients
* ASCO 2014:
Responses to Romidepsin by line of therapy in relapsed/refractory peripheral T-cell lymphoma
About HDACs - using plainer language  

 

 

May 27 - Approaching ASCO

* PAL update to ALLO SCT page:
ASCO 2014: Allo SCT in a cohort of 314 advanced lymphoma patients
* PAL update:  Find trials  by type of AGENT  Crizotinib for lymphoma

* PAL update:
Watch and Wait Expert comment on question if can you wait too long?
Watchful Waiting and Monitoring Indolent Lymphomas
* The utility of restaging bone marrow in PET-negative
DLBC lymphoma and baseline bone marrow involvement. http://1.usa.gov/1hZXm3T 

If further validated, DLBCL practice guidelines and response criteria could be modified so that BM biopsy is no longer required to document CR if the restaging PET-CT is negative.
PAL update:  Talking with your children about your cancer
* PAL update to Rituxan topic:
Association between rituximab use and progressive multifocal leukoencephalopathy  from VA database
* PAL update
Epigenetic agents for lymphoma
Honing in on the (epi)genetic basis of AITL

In this issue of Blood, Odejide et al report on recurring mutations in a large series of patients with angioimmunoblastic T-cell lymphoma (AITL) clustering around three epigenetic modifiers: TET2, DNMT3, and IDH2.1
* Gene Therapy: Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19 http://1.usa.gov/1nNtvQI

"The patient's lymphoma underwent a dramatic regression, and B-cell precursors were selectively eliminated from the patient's bone marrow after infusion of anti–CD19-CAR-transduced T cells. Blood B cells were absent for at least 39 weeks after anti–CD19-CAR-transduced T-cell infusion despite prompt recovery of other blood cell counts. Consistent with eradication of B-lineage cells, serum immunoglobulins decreased to very low levels after treatment. The prolonged and selective elimination of B-lineage cells could not be attributed to the chemotherapy that the patient received and indicated antigen-specific eradication of B-lineage cells. Adoptive transfer of anti–CD19-CAR-expressing T cells is a promising new approach for treating B-cell malignancies."
* For advocates:  NCI Cooperative Group Phase 3 Treatment Trials Historical Accrual Experience of Trials Activated 2000-2010 -- Preliminary Assessment of the DCTD/CTEP Slow Accruing Guidelines for Phase 3 Treatment Trials http://1.usa.gov/RawEyT

An important summary report for advocates and researchers -- to help identify in advance what kinds of trials or study designs are unlikely to succeed in accruing patients - will waste money and not answer questions of importance to patients.

*  A National Cancer Clinical Trials System for the 21st Century

Reinvigorating the NCI Cooperative Group Program
From iom.edu: http://bit.ly/1rS7Kzg

* PAL update:
Excellent Chemocare resources added to Side Effects page

   - Chemotherapy index  http://bit.ly/1fvcEBU

   - Common Chemotherapy Acronyms, Regimens, and Abbreviations http://bit.ly/PQBIY1

An excellent job done on listing and explaining side effects for cancer treatment agents - formatted very similar to NCI informed consent template.  Provides also information on when to notify your doctor and how the drug is thought to work.

* PAL updates:
Trials of Interest
 - Three T-cell lymphoma trials added based on report published in Blood

Monday, April 28

Please feel free to share items of interest with us -- or your questions -- by sending an email to support.

News items and updates posted to PAL topic pages:

* PAL updates: Trials of Interest

A resource we update fairly regularly. We checked the click counts for the types listed below and moved a good many studies to a new section ... because they have completed enrollment and are no longer recruiting participants.
For follicular
http://www.lymphomation.org/study-spotlight.htm#FL

For mixed types, b and t-cell, Hodgkin's:
http://www.lymphomation.org/study-sp...nhl-many-types
Nivolumab and Ipilimumab (two immune-checkpoint agents) in Hematologic Malignancy - ClinicalTrials.gov http://1.usa.gov/1m68liG
For DLBCL
http://www.lymphomation.org/study-spotlight.htm#DLBCL 
* PAL update:  Risk factors
New item on immune suppression from organ transplant as a substantial risk factor for DLBCL
* Anticancer Agents - My Cancer Genome http://bit.ly/1powkfa
* PAL update:
Alison J. Moskowitz, Matthew A. Lunning and Steven M. Horwitz
How I treat the peripheral T-cell lymphomas  T-cell lymphomas - background articles

 

Monday, April 21

Please feel free to share items of interest with us -- or your questions -- by sending an email to support.

News items and updates posted to PAL topic pages:

* PAL update:
PET for interim response to treating aggressive T-cell lymphoma?  PET imaging
* Cancer Biol Med. Mar 2013
Reduced-intensity conditioning allogeneic stem cell transplantation in malignant lymphoma: current status
Posted to Transplant  

In this article, we review the recent literature on RIC-allo-SCT as a treatment for major lymphoma subtypes. Areas that require further investigation in the context of clinical trials are also highlighted.
* April 2014: ASCO
Launches New Survivorship Guidelines Posted to Support

evidence-based clinical practice guidelines on the prevention and management of common symptoms that affect a large number of cancer survivors — neuropathy, fatigue, and depression and anxiety.
* PAL update:
Biomarkers and perspectives on this important aspect of clinical research
biomarkers to guide clinical decisions
* PAL  update Quality of Life
as endpoint in clinical studies but also as a routine tool to monitor the whole patient.

New public domain instrument added QOL instruments
* Video: NCI Clinical Trials and Translational Research Advisory Committee (CTAC) - March 2014
http://videocast.nih.gov/summary.asp?Live=13664&bhcp=1

For advocates: an important review of NCI Clinical trials (budget, outcomes, challenges.  It is long and starts slowly, but is worth it.
* Blood, 2013:
Determining Cell-Of-Origin Subtypes In Diffuse Large B-Cell Lymphoma Using Gene Expression Profiling On Formalin-Fixed Paraffin-Embedded Tissue – An L.L.M.P.P. Project
Diffuse Large Cell Lymphomas - In the News
 

Wednesday, April 9

*  PAL update by Linda
Abbreviations by categories added
* PAL draft
 
Critical Funding of NCI Cooperative Group studies are in jeopardy due to sequester cuts and change in NIH priorities

* PAL update: our manuscript submitted to ASCO Post
Perspective on the Patient-selected Controlled Trial by Karl Schwartz and Dr. Jim Omel PCT-proposal-4-3-14.pdf
* PAL perspective (draft)
Quality of Life Endpoints in clinical trials
Advocacy issues

Wednesday, April 2

* Refining Modern Transplant Therapy:
Jim Omel: "we owe a deep amount of gratitude to the patients that went before us" - http://bit.ly/1dR52JB 

Comment from viewer: Thank you for posting. I am better understanding the importance of participation in clinical trials. I do think some of us are scared off by the incorrect assumption that we may be assigned to the "placebo" arm, thus receiving no treatment, or possibly be given an inferior one. Some of those research studies that we learned about in PSYCH 101 come to mind. We do owe a tremendous amount of gratitude to those brave souls that participated in previous trials, and I am now motivated to do my part for future generations.
 
* Onclive 2014: video
Experts discuss Novel ADCs in Development for Lymphoid Malignancies antibody-drug conjugates - in the news 

We learn here that there's much to learn yet about the role of antibody-drug conjugates - such as the importance testing these active agents with other drugs that do not have overlapping toxicity.
*  Funding of NCI Cooperative Group studies are in jeopardy due to sequester cuts

Warnings and concerns by NIH Director Francis Collins are coming to pass:
Medical research at risk - POLITICO.com http://politi.co/1oqvtKs

A note received last week from a leading investigator: 

We are at an Executive and Board of Directors meeting of the Alliance this weekend. The issue of funding, collaboration, reality, and strategies has been discussed at length. ASCO is also very engaged. Advocate and active patient involvement is critically important, probably more than ever.

If you are enrolled in an NCI trial the continuation of therapy may be put in jeopardy if funding is not adequate.  Please contact us and we will forward your email to leaders in the cooperative group research - allowing you to give voice to your concerns.
* PAL advocacy update
Background on oral drug parity bill and how to inform your representative about your views on this.
* PAL update: patient recommended oncologist
Added
Dr. Ann LaCasce to North East oncolgists based on a patient recommendation (and expert videos)
* PAL update: conspiracy by BigPharma?
Are natural compounds at a disadvantage because they cannot be patented?

(Your comments are still needed)
* PAL update: CLL page
New roles defined by NCCN for Obinutuzumab for CLL in the News

 

Monday, March 31

* PAL update: conspiracy by BigPharma?
Are natural compounds at a disadvantage because they cannot be patented?
* PAL update:  CAM item
Science Bloggers write about DCA for cancer
* Fever of unknown origin (FUO) caused by multiple myeloma: The diagnostic value of the Naprosyn test http://bit.ly/1lhI2Tz

 

Thursday, March 27

* PAL draft:
Perspective on Industry versus Publicly-funded Research
* PAL update:
Symptoms of lymphoma - about and how to report  symptoms.htm
* PAL update:
BJM 2014: Report on Vorinostat in relapsed indolent B-cell non-Hodgkin lymphoma and MCL -
Posted to In the News - About HDACs  
* PAL update:
Immunotherapy of Malignant Disease Using Chimeric Antigen Receptor Engrafted T Cells
Posted to CAR News and Reports

 

Friday, March 21

* J of Oncology Practice 2014:
Is It OK to Fire My Oncologist? http://bit.ly/1h4BW4k 

JPO: Is It OK to Fire My Oncologist - PDF? http://bit.ly/1h6tnGl
* PAL update:
Marginal Zone Lymphoma - description and natural history ... also associations with infectious disease
 MZL Nodal section
New reports on therapeutics and how it is treated - including treatment of Hepatitis C virus
* PAL update:
CLL TREATMENT REPORTS in the news

Comment: Unprecedented advances in so short a time.
* The ASCO Post:
Promising results for Brentuximab (cd30 antibody-drug conjugate) in Cutaneous t-cell lymphoma http://bit.ly/1l9XFz3
* PAL update:
Living well with lymphoma - how to manage anxiety
* PAL update:
Medscape, free login required:

Time for 'Smaller and Smarter' Clinical Trials, Says ASCO Recipe for Progress Against Lymphoma

In many cases, however, targeted agents are being developed without a complete understanding of the drug's target and without a companion diagnostic tool to help in the selection of appropriate patients, he and his colleagues point out.

To address that issue, the working groups recommend that trial sponsors establish comprehensive biospecimen banks, with informed consent from patients, so that investigators can "ask scientific questions before and after trials are completed" that will facilitate the discovery and validation of biomarkers.
* PAL:
Why PAL - movie (early draft)  MPG
* Brit J Haematol 2014:

Lenalidomide plus rituximab can produce durable clinical responses in patients with relapsed or refractory, indolent non-Hodgkin lymphoma. Posted to Lenalidomide page with comment
 * Idelalisib (PI3k inhibitor), in relapsed refractory indolent Non-Hodgkins Lymphoma? [Blood. 2014] -
PAL topic on PI-3-kinases  
 

Friday, March 13

News items and updates posted to PAL topic pages:

* Brit J Haematol 2014:

Lenalidomide plus rituximab can produce durable clinical responses in patients with relapsed or refractory, indolent non-Hodgkin lymphoma. http://1.usa.gov/Op7WsM 
* PAL many more updates to the A to Z index of lymphoma topics
A to Z Lymphomation.org
* PAL - New trial added to Trials of Interest
Ibrutinib + Lenalidomide, With and Without Rituxan for Relapsed/ Refractory DLBC Lymphoma
Clinical Trials of Interest
* PAL:
Drug use, balancing risks and benefits - 5 questions to ask
* PAL:
2 Idelalisib reports in the news ... for CLL and NHL in relapsed / refractory setting - with comments
PAL PI3K inhibitor - Idelalisib
* PAL:
Pain management
 

Thursday, March 13

* PAL update:
Microenvironment PAL

updated explanation including role of PD1 signaling as a way tumors evade the immune system that can be targeted with therapy.
* ASCO Post: Viewpoint:
Molecular Profiling Improves Classification of
Nodal Peripheral T-Cell Lymphomas - Horwitz, MD
Posted to PAL - T-cell lymphomas
* HemOnc Today 2014:
R-CHOP plus radiation improved outcomes in elderly patients with bulky B-cell aggressive lymphoma
 Posted to Diffuse Large Cell Lymphomas

* Psych Central 2014:
7 Tips for Authentic Engagement in an Online Support Community Support Groups

* IDF (Immune Deficiency Foundation)
Immunoglobulin Therapy & Other Medical Therapies for Antibody Deficiencies
Posted to Resources for Labs- immunoglobulins

* National Cancer Institute
Cancer Myths and Misconceptions:
Posted to Common Myths  

"Can cancer surgery or a tumor biopsy cause cancer to spread in the body? For the answer to this and other common questions…"
 

Sunday, March 9

Select "lymphomation" items posted by Anjou, Carol, and Karl for Patients Against Lymphoma - sometimes with comment.
Please feel free to share items of interest with us -- or your questions -- by sending an email to support.

* J CLin Onc 2014:
The Kafkaesque Process of Cancer Diagnosis http://bit.ly/1npoPQI 
*HemOnc Today 2014:
R-CHOP plus radiation improved outcomes in bulky B-cell lymphoma http://bit.ly/1cJKpyq

*Psych Central 2014:
7 Tips for Authentic Engagement in an Online Support Community http://bit.ly/1ib4rl2

Comment Title: An exciting concept


* NEJM:
Engineering Cellular Resistance to HIV http://www.nejm.org/doi/full/10.1056/NEJMoa1300662

Mark A. Kay, M.D., Ph.D., and Bruce D. Walker, M.D.

Now this knowledge, originally derived from a clinical observation, has led to another important step forward. In this issue of the Journal, Tebas et al.3 report on the successful adoptive transfer, in patients with HIV infection, of autologous CD4 T cells in which the gene encoding CCR5 is knocked out. In a study designed to examine the safety and tolerability of targeted genome editing in humans with HIV infection, the investigators found that the genetically modified cells persist in vivo with a half-life of nearly a year; they also appear to be protected from HIV infection, because when antiretroviral therapy (ART) is stopped, they are depleted at a slower rate than are unmodified cells.


Comment:

A creative approach. One can imagine also gene editing of autologous t-cells such that the engineered cells are deaf to immune checkpoint signals of the malignant cells as a novel immunotherapy for cancer.

* J CLin Onc 2014:
The Kafkaesque Process of Cancer Diagnosis http://bit.ly/1npoPQI

 
* NEJM:
Beyond Repeal — A Republican Proposal for Health Care Reform — http://bit.ly/1h4TCOu
* PAL update:
 Sugar restriction to fight cancer?  PAL
* Cancer Genetics Incorporated
Complete Program- CLL and DLBCL Testing Services  http://bit.ly/NNZGm7

COMMENT:  The need to validate the risk factor is very important ... so what is lacking in the resource are Level of Evidence scores .. as some markers may be exploratory at this point ... or the significance can vary because there are other (perhaps not yet known) biological risk factors that are at work influencing how the disease behaves / responds to therapy.      So actual behavior and staging could well trump the results of a test.   For example,  the IHC method for determining ABC / GCB DLBCL is not considered reliable as a way to select patients for investigational protocols based on cell of origin.  (Karl)      

 

Saturday, March 8

* KevinMD 2014:
6 things not to do as a caregiver http://bit.ly/NKZnbY

* J CLin Onc 2014:
The Kafkaesque Process of Cancer Diagnosis http://bit.ly/1npoPQI

* NY Times 2014:
Living With Cancer: Finding Calm in the Storm http://nyti.ms/1e7V7te

* Science Based Medicine 2014:
The illusions of “right to try” laws http://bit.ly/1ifmqJw

* ABC News 2014:
Why I Don’t Mind Being a Human Science Experiment for Cancer Research http://abcn.ws/1nnuLcS

* MNT 2014:
How the internet is transforming our experience of being ill http://bit.ly/1cHQBRJ

* Science Daily 2014:
B-cells aggravate autoimmune diseases http://bit.ly/NXvDs6

Interesting -- perhaps this is part of why there is more risk of lymphoma in folks who get autoimmune things?
 

Friday, March 7

Select "lymphomation" items posted by Anjou, Carol, and Karl for Patients Against Lymphoma - sometimes with comment.
Please feel free to share items of interest with us -- or your questions -- by sending an email to support.

* ACS:
Placebo and Nocebo Effect explained  http://bit.ly/1oxm0vG

"A change in a person’s symptoms as a result of getting a placebo is called the placebo effect. Usually the term “placebo effect” speaks to the helpful effects a placebo has in relieving symptoms. This effect usually lasts only a short time. It’s thought to have something to do with the body’s chemical ability to briefly relieve pain or certain other symptoms."

COMMENT:  If there's any placebo effect for cancer or its treatment the effect is very small and rare, otherwise placebo-controlled trials would be considered ethical for studies of cancer therapies (they are not).

The notion that belief matters can put a lot of stress on the patient ... as in: I did not do well because I was not positive enough. We start to worry about worrying. And if we do poorly we blame ourselves instead the real culprit - bad luck, in having a cancer with a biology that was resistant to treatment. This topic is covered well in an article called the Tyranny of Positive Thinking. (Karl)
* Ann Behave Med, 2010:
Positive Psychology in Cancer Care: Bad Science, Exaggerated Claims, and Unproven Medicine http://1.usa.gov/1hTm2xH

"Claims about these areas of research routinely made in the positive psychology literature do not fit with available evidence. We note in particular the incoherence of claims about the adaptational value of benefit finding and post-traumatic growth among cancer patients, and the implausibility of claims that interventions that enhance benefit finding improve the prognosis of cancer patients by strengthening the immune system."

Thursday, March 6

* Helio 2014:
Subcutaneous rituximab non-inferior to IV formulation in follicular lymphoma http://bit.ly/1f9R2nZ

Patients underwent one initial dose of IV rituximab in the first cycle, and they went on to receive their assigned therapeutic regimens for cycles two to eight.

Comment: This initial administration by IV is probably needed for safety as most infusion related side effects occur with the first cycle of Rituxan.  With IV administration you can slow down how fast you give Rituxan to avoid serious problems  (Karl)


* Cancer Research UK 2014:
Meat and cheese aren’t ‘as deadly as smoking’ http://bit.ly/1fHvYv3

* News Medical 2014:
Chemotherapy induces long-lasting epigenetic changes in survivors' blood cells http://bit.ly/1gRhS6O

Explains why some symptoms like fatigue may persist for months after chemo

* Lymphoma Hub 2014:
Positive outcomes with primary chemotherapy in PB-DLBCL http://bit.ly/1hJ3643

* Medical Xpress 2014:
Common cancers evade detection by silencing parts of immune system cells http://bit.ly/NVUM6y 

NOTE: An epigenetic agent discussed in this piece is being evaluated for the treatment of DLBCL Find trials

* Weill Cornell Medical College 2014:
Does palliative chemotherapy palliate? Findings suggest need for caution in use of chemotherapy among advanced cancer patients  http://bit.ly/NtUnIm

* MNT 2014:
Palliative chemotherapy: harms and benefits weighed in new study http://bit.ly/P0hHOZ

* Medscape 2014:
Palliative Chemotherapy Is 'Disingenuous Term,' Says Critic http://bit.ly/Nyy841
* Search of: Florida Studies
 for Lymphoma OR CLL - List Results - ClinicalTrials.gov http://1.usa.gov/1kyZfu3

 

Tuesday, March 4

* Search of: Florida Studies
 for Lymphoma OR CLL - List Results - ClinicalTrials.gov http://1.usa.gov/1kyZfu3
* Lymphoma Coalition
Q&A About Lymphoma (video) http://bit.ly/1coWaKn

Dr. Steven Horwitz, a medical oncologist at Memorial Sloan Kettering Cancer Center, answers questions about different types of lymphomas including non-Hodgkin lymphoma as well as treatments for rare lymphomas. He also discusses when watchful waiting should be considered as well as provides insights on survivorship and quality of life issues.
* Science Daily
Putting the brakes on immunity http://bit.ly/1coWHw3

“While the immune system's primary role is to fight infections, it can also become overactive, leading to problems like allergies and autoimmune diseases. Now researchers have discovered a powerful mechanism that keeps the system from "going rogue."

* IG Online
Working While Chronically Ill: Is It Possible? http://bit.ly/1cxWbGu

Some of our MALT members are on IVIG.

* University of Bristol News
Researchers identify innate channel that protects against pain (not lymphoma specific) http://bit.ly/1kPrSjp

“This ion channel, known as TREK2, is present in the membranes of these neurons, and the researchers showed that it provides a natural innate protection against this pain.”

* Journal, Mayo Clinic Proceedings
Contamination of Stethoscopes and Physicians' Hands After a Physical Examination http://bit.ly/Np1eTs 

“These results suggest that the contamination level of the stethoscope is substantial after a single physical examination and comparable to the contamination of parts of the physician’s dominant hand.”

* KevinMD, Gene Uzawa Dorio MD
What is the price of that medical test? http://bit.ly/1gN3rAH

Maybe we should shop around before getting that test...
*Oncology Times 2014:
Improved Access to Stem Cell Transplants for Elderly & Ethnic Patients http://bit.ly/1kpCWn9
* Medpage Today 2014:
RA-Lymphoma Risk: Biologics Not to Blame http://bit.ly/1fMzVNn
* Cancer Research UK 2014:
The link between cancer and infections http://bit.ly/1mBKoNq
* NYTimes 2014:
Can Doctors Be Taught How to Talk to Patients? http://nyti.ms/1hDVDSk
*Oncology Times 2014: 
View from the Other Side of the Stethoscope: Patient Handout—Supporting Your Children http://bit.ly/1gFvYYH
*Science Daily 2014:
Shingles: A common and painful virus http://bit.ly/1hsWTsI  

(note- vaccine not recommended for patients with lymphoma)
* News Medical 2014:
Researchers launch new programme to remotely monitor patients undergoing chemotherapy http://bit.ly/1o9baM7

Monday, March 3

Select "lymphomation" items posted by Anjou, Carol, and Karl for Patients Against Lymphoma - sometimes with comment.
Please feel free to share items of interest with us -- or your questions -- by sending an email to support.

* PAL update:  Index A-Z for lymphomation.org home page
Under development: www.lymphomation.org
* PAL update:
The ASCO Post: Standardizing the Interpretation of PET Scans:   Posted to PET scans

to assist in interpreting SUV numbers

*Leuk Lymph 2014:
Retreatment with Bendamustine-containing regimens in patients with relapsed/refractory chronic lymphocytic leukemia and indolent B-cell lymphomas achieves high response rates and some long lasting remissions. http://1.usa.gov/1clYVMq

*PR web 2014: Mayo
Study Finds Gene Mutation Common in Non-Hodgkin’s Lymphoma, Reports the Non-Hodgkin’s Lymphoma Center: http://bit.ly/1fROrDw

identification of a mutated gene frequently found in Non-Hodgkin’s Lymphoma may open the door to new treatments.

* Sunrise Rounds 2014:
My perfectly dull day - musings from an oncologist http://bit.ly/1fyPWI8

 * KevinMD 2014:
The conspiracy of cancer prognosis http://bit.ly/1pM75B6

* Dr Sharman's Blog 2014:
ASH 2013 Video wIth Andrew Schorr http://bit.ly/1fz3nSz

* Cancer 2014:
Combined lenalidomide, low-dose dexamethasone, and rituximab achieves durable responses in rituximab-resistant indolent and mantle cell lymphomas. http://1.usa.gov/1mPcUih

* PRweb 2014:
Study Finds Younger Non-Hodgkin’s Lymphoma Patients Undertreated for Neutropenia http://bit.ly/1n1ZrQH
* Worth repeating
ASCO Post: “Novel Agents Show Activity in relapsed Non-Hodgkin Lymphoma”
including CRs http://bit.ly/1dSn1gv
* Worth repeating, must read for research advocates 
FDA.gov:  Critical Path white paper - fda.gov: http://1.usa.gov/1fTo8gc

This report provides the Food and Drug Administration's (FDA’s) analysis of the pipeline problem — the recent slowdown, instead of the expected acceleration, in innovative medical therapies reaching patients.

 

Tuesday, February 25

Select "lymphomation" items posted by Anjou, Carol, and Karl for Patients Against Lymphoma - sometimes with comment.
Please feel free to share items of interest with us -- or your questions -- by sending an email to support.

* Reuters
Jury out on vitamins' use against heart disease, cancer http://reut.rs/MYePRF  

* The Health Care Blog 2014:
That Vitamin There Could Kill You http://bit.ly/1efVINr

* NPR 2014:
Scant Evidence To Support Vitamins Against Cancer, Heart Disease http://n.pr/1hutWeE

* Medscape 2014:
Dramatic Results With CARs in B-Cell Leukemia http://bit.ly/1fGTYZM

Cd19 CAR T-cell therapy  Find trials 
* U Penn 2014:
Cancer patients turning to mass media and non-experts for info:
Increasing inappropriate use of high-cost advanced imaging procedures http://bit.ly/1k6mAD2

* Onc Times 2014:
CLL: Debating the Choice of Chemo-Immunotherapy http://bit.ly/1gsxsXV

* Onc Times 2014:
New Alliance Aims to Accelerate Success of Biomarkers in Clinical Practice http://bit.ly/1bHCbpD

* J Clin Onc 2014:
Event-Free Survival at 24 Months Is a Robust End Point for Disease-Related Outcome in Diffuse Large B-Cell Lymphoma Treated With Immunochemotherapy. http://1.usa.gov/1k5zC3C

* Leuk Lymph 2014:
Excellent outcomes for adolescents and adults with acute lymphoblastic leukemia and lymphoma without allogeneic stem cell transplantation - The FRALLE 93 pediatric protocol. http://1.usa.gov/1ebfJVb

* Leuk Lymph 2014:
Prolonged Progression-Free Survival and Preserved Quality of Life in the Canadian Prospective Study of Tositumomab and Iodine131-Tositumomab (TST/I131-TST) for Previously Treated, Rituximab-exposed, Indolent non-Hodgkin Lymphoma. http://1.usa.gov/MUITxm

* Science Blogs 2014:
GMO virus vs B-Cell Acute Lymphoblastic Leukemia:
Why is this not a standard therapy yet?? http://bit.ly/1mDeLq9

* Science Daily:
New paradigm in cancer immunotherapy: Awakening the body's immune system to kill cancer metastases http://bit.ly/1drNfCp

* News Medical 2014:  RIT in newly dx'd patients
Scientists show promising results for new treatment approach in follicular lymphoma http://bit.ly/OyUGCO

* Science Based Medicine 2014:
Depression Re-examined: A New Way to Look at an Old Puzzle http://bit.ly/1jxmLEA

 Not related to lymphoma, but anjou finds interesting....

* Leukemia Research 2014:
The lower peripheral blood lymphocyte/monocyte ratio assessed during routine follow-up after standard first-line chemotherapy is a risk factor for predicting relapse in patients with diffuse large B-cell lymphoma http://bit.ly/1ck6nCj

* KevinMD
What to do if your doctor isn’t polite. Here’s a question I’m almost afraid to ask: when you go to a doctor (not one you see all the time), does the doctor usually introduce himself (or herself) and explain what they are there to do? And, do they sit down? I really hope that you are answering yes … but I know that…
http://bit.ly/1gxChO7
* KevinMD
Do patients value their health information privacy? http://bit.ly/NstpAN
* KevinMD
Why is American health care so expensive? http://bit.ly/1hj9Bu0

* Cancer blog from MD Anderson Cancer Center
6 ways to cope with chemobrain - Cancerwise http://bit.ly/1hiXEog
* KevinMD
 Are physicians ready for the e-patient movement? http://bit.ly/1msnGr7

The “awakening” of the e-patient has been tied to the seriousness of the medical condition one has been diagnosed with. As described in the e-patient white paper, when one develops a more severe medical condition, they are more likely to adopt a higher level of medical knowledge enabling a more competent and in control persona, which is associated with greater assertiveness and autonomy with medical providers.
 

Monday, February 24

* WSJ.com
How to Bring the Price of Health Care Into the Open http://on.wsj.com/1jtW17R
* CDC
Flu Symptoms & Severity  http://1.usa.gov/1dpeU71
* Advisory Committee: It's about deciding on a close call
An advocate's experience of one such deliberation  PDF
* PAL update: "Evasion and suppression of immunity" added to Hallmarks of Cancer
Lymphoma simplified  PDF 

Well, maybe not a terribly simple explanation, but one we feel good about. 
A printable brochure for the purpose of increasing public and patient understanding of lymphoma.  
* News Medical 2014:
Cell therapy: A powerful treatment for cancer patients http://bit.ly/1lfaZBU

* Science Daily 2014:
Earlier palliative care improves quality of life, patient satisfaction, cancer study shows http://bit.ly/1e1wIsX

* Science Daily 2014:
Lymphoid cells discovered in human spleen, essential for production of antibodies http://bit.ly/1k5l3NA

* PRweb 2014:  cutaneous T-cell lymphoma (CTCL)
Combination of a psychiatry drug with a photo-sensitizer may work “synergistically” in patients with a certain kind of Non-Hodgkin’s Lymphoma. http://bit.ly/OtGZ8a

* The Atlantic 2014:
Even as a Doctor With Decent Insurance, I Had Difficulty Entering the Healthcare System:
Why navigators benefit everyone http://bit.ly/1pjTpgs
 

Saturday, February 22

* LIVESTRONG.COM
Blood Clot in Arm Symptoms | http://bit.ly/1mnW1aK
* Ibrutinib: full prescribing information
(Label - recently approved for relapsed MCL and CLL)
From accessdata.fda.gov: http://1.usa.gov/1fkjyqY 
*  PAL update: Clinical Trials of Interest

(posted new trials of interest to lymphoma and CLL groups.)

* Safety Study of Anti-LAG-3 in CLL, HL and NHL - Full Text View - ClinicalTrials.gov http://1.usa.gov/1l9mzyi

anti-LAG-3 monoclonal antibody BMS-986016
A monoclonal antibody directed against the inhibitor receptor lymphocyte activation gene-3 (LAG-3), with potential immunomodulating and antineoplastic activities. Upon administration, the anti-LAG-3 monoclonal antibody BMS-986016 binds to LAG-3 on tumor infiltrating lymphocytes (TILs). This may activate antigen-specific T-lymphocytes and enhance cytotoxic T cell-mediated tumor cell lysis, which would lead to a reduction in tumor growth. LAG-3 is a member of the immunoglobulin superfamily (IgSF) and binds to major histocompatibility complex (MHC) class II. LAG-3 expression on TILs is associated with tumor-mediated immune suppression.  (NCI Thesaurus)

The sponsor is also studying this agent in combination with its PD-1 antibody, which targets immune checkpoints.

 

Friday, February 21

Select "lymphomation" items posted by Anjou, Carol, and Karl for Patients Against Lymphoma - sometimes with comment.
Please feel free to share items of interest with us -- or your questions -- by sending an email to support.

*  Feature video - Medscape 2014:
FDA Sends Valentine to CLL Patients (Cheson video on importance of ibrutinib) http://bit.ly/1cXxfYB
* ASCO Post: “Novel Agents Show Activity in relapsed Non-Hodgkin Lymphoma” - including CRs http://bit.ly/1dSn1gv
Promising reports in this article - impressive outcomes (CRs) particularly for single agents in relapse setting.

SAR 245409 is a potent oral pan-inhibitor of PI3K

     * Lymphoma OR CLL | SAR 245409 - List Results - ClinicalTrials.gov http://1.usa.gov/1hyV6Wi

copanilisib (BAY 80-6946), is an intravenously administered compound that has significant activity against alpha and delta isoforms of PI3K; the delta isoform has a role in B-cell signaling, development

      * Lymphoma OR CLL trials for BAY 80-6946 (copanilisib) ClinicalTrials.gov http://1.usa.gov/1glACLs

PNT2258 DNAi molecule targets the noncoding, nontranscribed regulatory region of the Bcl2 gene.

       * Lymphoma OR CLL | PNT2258 - List Results - ClinicalTrials.gov http://1.usa.gov/1nQQad1 
* Management of chronic pain in the elderly:
focus on transdermal buprenorphine http://1.usa.gov/1jkKiIN (Posted also to Pain topic)

Thursday, February 20

Select "lymphomation" items posted by Anjou, Carol, and Karl for Patients Against Lymphoma - sometimes with comment.
Please feel free to share items of interest with us -- or your questions -- by sending an email to support.

*  Medscape 2014:
FDA Sends Valentine to CLL Patients (Cheson video) http://bit.ly/1cXxfYB

* Hebrew Univ of Jerusalem 2014:
New treatment proposed to prevent intestinal inflammation in cancer patients: Research team headed by Hebrew U. scientists http://bit.ly/1ffiQv6

Scientists think an existing drug may help prevent mucositis from chemo-- research to be done.

* Leuk Lymphoma 2014:
Prolonged Progression-Free Survival and Preserved Quality of Life in the Canadian Prospective Study of Tositumomab and Iodine131-Tositumomab  (TST/I131-TST) for Previously Treated, Rituximab-exposed, Indolent non-Hodgkin Lymphoma. http://1.usa.gov/1mr4UUy

93 patients with >2 lines of therapy, responding to last treatment, were enrolled at 12 Canadian centres. Median age, disease duration and number of prior therapies (#PTx) were 59 years, 4.9 years and 5, respectively. Outcomes were response rate (43.0%), median progression free survival (mPFS) (12.0 months), 5-year PFS (27%), and median overall survival (OS) (59.8 months).

* Patient Power 2014:
Targeted Approaches to Treating Lymphoma http://bit.ly/1mppZ1C

* Brian Koffman's Blog 2014:
ASH 2013: Jan Geissler & Giora Sharf Part 2 on Adherence,
the High Cost of Cancer Medications, and the Importance of Clear Communication  http://bit.ly/1mpZ4Ti

* NY Times 2014:
Itching: More Than Skin-Deep http://nyti.ms/O45zfn

 General article on itching, not lymphoma specific.

* University Health Network 2014:
Cancer study shows earlier palliative care improves quality of life, patient satisfaction http://bit.ly/1eOMWRB

* Bio Blood Marrow Transplanplant 2014:
Pre-Transplant FDG-PET Scan Lacks Prognostic Value in Chemosensitive B-Cell Non-Hodgkin Lymphoma Patients Undergoing Non-Myeloablative Allogeneic Stem Cell Transplantation. http://1.usa.gov/1gFr0NO
 

Monday, February 17

Select "lymphomation" items posted by Anjou, Carol, and Karl for Patients Against Lymphoma - sometimes with comment.
Please feel free to share items of interest with us -- or your questions -- by sending an email to support.

* Medscape, 2013:
Significant Off-Label Chemo Use in Elderly Cancer Patients http://bit.ly/1bfpP7W
* Patient Power 2014: video with Dr Sharman
What to Consider When Choosing a CLL Treatment Path http://bit.ly/1f1DpNk 

* Science Daily 2014:
Potential therapy for rare, drug-resistant cancer using already-approved drugs http://bit.ly/1gsLPMz

* Blood 2014;
Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation.  http://1.usa.gov/1mj9lAu

* Science Daily 2014:
Cancer doctors have opportunities to cut costs without risk to patients, experts say http://bit.ly/1fp1JU2

* Bone Marrow Transplant 2014:
Matched unrelated donor allogeneic transplantation provides comparable long-term outcome to HLA-identical sibling transplantation in relapsed  diffuse large B-cell lymphoma. http://1.usa.gov/1mj9CDN

* Leuk Lymphoma 2014:
Recent Advances In Mantle Cell Lymphoma: Report of the 2013 Mantle Cell Lymphoma Consortium Workshop. http://1.usa.gov/1kJzp6d 

abstract not particularly informative but some might be interested in requesting the full article from the author or publisher

* KevinMD 2014:
Palliative care: The first conversation http://bit.ly/MWCSzU

not an easy read, direct discussion of end of life

*Forbes 2014:
More Proof The Flu Vaccine Works (Abelpharmboy) http://onforb.es/1oEjmXQ

Important to follow oncologists vaccine recommendations and for those around folks going through chemo to get vaccinated...
 

 

Sunday, February 16

Select "lymphomation" items posted by Anjou, Carol, and Karl for Patients Against Lymphoma - sometimes with comment.
Please feel free to share items of interest with us -- or your questions -- by sending an email to support.

* PAL: update
 bone marrow involvement topic page
* Your Questions About The Affordable Care Act : NPR http://n.pr/1j4eLeb

A comprehensive list of questions and answers provided here
* Gene Silencing with Small RNAs — Peter Waterhouse, ISS2013 - YouTube http://bit.ly/1f5AAJk

Put your feet up and enjoy this amazing presentation on the science.
* Dr Sharp:
Roles of RNA in Gene Regulation - YouTube http://bit.ly/1lTFWcs
* Now to a clinical application of targeting microRNA (gene regulators):
Abstract LB-250: Development of a miR34-based cancer therapy. -- Daige et al. 73 (1008): LB-250 -- Cancer Research http://bit.ly/1f1wO5w  
* PAL query:
Open Studies | Lymphoma OR CLL | microRNA - List Results - ClinicalTrials.gov http://1.usa.gov/1kJXKZC
* ASCO Post:
“Major Cancer Advances in 2013 Highlight Importance of Federal Funding” http://bit.ly/1dzCa1p
* PAL:  An advocate's perspective:  
Ownership of an Investigational Drug Comes with Unique Responsibilities PAL
* Final Rules for Expanded Access to Investigational Drugs for
Treatment Use and Charging for Investigational Drugs http://1.usa.gov/1b7ekiJ
 

Friday, February 14

Select "lymphomation" items posted by Anjou, Carol, and Karl for Patients Against Lymphoma - sometimes with comment.
Please feel free to share items of interest with us -- or your questions -- by sending an email to support.

* The Atlantic 2014:
Plight of a Young Cancer Survivor: When young adult cancer patients beat the disease, fear of recurrence and even post-traumatic stress disorder can become their new normal. http://bit.ly/1c4tR19

* Helio 2014:
Post-induction PET indicated risk for progression in follicular lymphoma http://bit.ly/1czZwEG

“In follicular lymphoma patients, post-induction PET substantially modified response assessment and is strongly predictive for the risk of progression,” the researchers wrote. “PET should be considered in further updates of response criteria.” ... a tool to potentially guide clinical decisions, such as the need to have maintenance. (Karl)
* KevinMD 2014;
Some patients don’t expect doctors to be miracle workers  http://bit.ly/1c1ZCId

What these patients tell me they most appreciate is a physician who will not stop caring and trying to be helpful.

* Oncology Times 2014:
CLL: Debating the Choice of Chemo-Immunotherapy : Oncology Times http://bit.ly/1gsxsXV

A good read


 

Thursday, February 13

Select "lymphomation" items posted by Anjou, Carol, and Karl for Patients Against Lymphoma - sometimes with comment.
Please feel free to share items of interest with us -- or your questions -- by sending an email to support.

* PAL - research advocacy
Our following comment received good initial feedback for Steering committee

As always, the feasibility of completing a study is an important consideration - which is especially challenging for diseases with many effective treatments and competing investigational protocols. So I feel that the committee should be alert to opportunities that are based on unique clinical settings and needs.  ... For example, patients with untreated indolent lymphoma with low tumor burden. Having no immediate need to treat or to achieve a fast response, this population provides a unique opportunity to evaluate lower-risk protocols that are unlikely to burn treatment bridges. In the past, vaccine studies accrued very rapidly (Stanford idiotype w&w trial), showing that patients will readily contribute tissue for the chance to participate in immunotherapy studies. Tissue acquired in this population could be used to select patients likely to respond to immune checkpoint antibodies (for example), and help also to develop prognostic biomarkers to understand the very different and unpredictable clinical courses of this disease.

* KevinMD 2014;
A cancer patient return visit after 20 years http://bit.ly/1c1ZCId

*Oncology Times 2014:
CLL: Debating the Choice of Chemo-Immunotherapy : Oncology Times http://bit.ly/1gsxsXV

* Dr Sharman 2014:
Irbrutinib has been approved in CLL http://bit.ly/1gsmtxG

* Brian Koffman's blog 2014:
YEAH! Ibrutinib (Imbruvica) is Approved for CLL http://bit.ly/1dJutpp

Note:  An important issue for patients will be the very high out of pocket cost for this oral cancer drugs, which can effectively deny access to patients with low and fixed income (many seniors).  

The company has announced plans to assist patients indirectly (Sharman http://bit.ly/1nhoZI0 ), however there are nagging questions, such as will the company include Medicare patients (seniors) in such programs ( See for background on company policy http://bit.ly/1cfCwL0 ... Further:

What percentage of patients will find the programs that help with cost?

What are the details about these programs? (Does it help for a month, a year, or three years?)

If everyone had access to the programs, how long would the industry continue to provide it on a voluntary basis?

* Blood 2014:
An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era http://bit.ly/1jzqpQY

* Oncology Times 2014:
View from the Other Side of the Stethoscope: Twin Challenges—Kids and Cancer http://bit.ly/1eRfO1I 
Discusses how an oncologist can help a patient who has children.

* ahip.org, April 25, 2013:
Comprehensive Assessment of ACA Factors That Will Affect Individual Market Premiums in 2014 http://bit.ly/1md7vB8

* Cancer Network:  Yes, it is worth getting past the ad
Experts Say Palliative Care Underused in Cancer Care  http://bit.ly/1lIKgLy

Wednesday, February 12

Select "lymphomation" items posted by Anjou, Carol, and Karl for Patients Against Lymphoma - sometimes with comment.
Please feel free to share items of interest -- or your questions -- by sending an email to support.

* J Clin Onc 2014:
Mature Results of a Phase II Study of Rituximab Therapy for Nodular Lymphocyte-Predominant Hodgkin Lymphoma. http://1.usa.gov/1aUPT8d  Posted to HL page

* Dr Sharman 2014: (requires log in to read the CME program)
Management of High Risk CLL http://bit.ly/1hbPRf3 

* Hemonc today 2014:
Idelalisib active in heavily pretreated indolent NHL http://bit.ly/1fXK0oo

See also Idelalisib / GS-1101 (formerly CAL101)  Find trials

* Onclive 2014:
Six Targeted Agents for CLL Command Spotlight at ASH http://bit.ly/1gjDTw8

* Respectful Insolence 2014:
Stanislaw Burzynski and the cynical use of cancer patients as shields and weapons against the FDA, this time with rock stars
http://bit.ly/1jxbRBj
* New Scientist 2014:
Kids miss out on cancer drugs because of lack of trials http://bit.ly/1fXMzXv
* New PAL trial queries* added to Find Trials by Type of Lymphoma and Treatment status

   untreated "Hodgkins lymphoma" pediatric  - ClinicalTrials.gov http://1.usa.gov/1eU3Z9s
   relapsed "Hodgkins lymphoma" pediatric - ClinicalTrials.gov http://1.usa.gov/1cwbvmz

NOTE: PAL trial queries are commands that lists specific types of studies on ClinicalTrials.gov.  Using the same query will show new studies next month or year. 

The goal is to make it easier for the community (patients, caregivers, and physicians) to locate trials that may be appropriate for different clinical situations and types of lymphoma. 

TIP: After you click the query, you can click the
On a Map tab to show where the trials are taking place on a map.


 

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