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Treatments > Outcome abstracts

Last update: 02/28/2013

Treatment Controversies | Treatment Review Articles     
Can we Cure indolent lymphomas?
| Comparing Protocols 
Rituxan as single agentChemo-Rituxan-based  | Fludarabine-Rituxan-based |
 Stem Cell-based | Radiotherapy | Radio-immunotherapy-based | Vaccine-based

Also see:  Treatment Overview  |  Evaluating Medical Claims and Data: Lymphomation.org
and Jay Gould's encouraging essay: The Median isn't the Message

NOTE: Single arm studies that provide response rate and duration of response cannot tell us which protocols are superior.  These measures alone can't take into account different risk factors in the study population or how the responses were assessed over time.
 
For indolent lymphomas, there's considerable controversy regarding the best approach to treatment and in most cases there is no gold standard of care.  The queries of ClinicalTrials.gov below will show promising protocols that are currently being tested in head-to-head randomized studies, which is the best tool we have for judging the relative strengths and weaknesses of available protocols, and for making progress against lymphomas.  ~ KarlS

Randomized phase III studies for lymphoma or CLL

Treatment 
controversies 

Review articles

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TOPIC SEARCH: Web

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Bendandi:

Aiming at a curative strategy for follicular lymphoma.
CA Cancer J Clin. 2008 Sep-Oct;58(5):305-17. Epub 2008 Aug 28.
PMID: 18755938 

"One clear fact is that no patients will ever be cured by adopting a palliative treatment approach. The assumption that patients with follicular lymphoma are incurable is certain to be a self-fulfilling prophecy. Here the author summarizes the large and growing body of knowledge that suggests an expectant approach to management is not appropriate for all patients.
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Cabanillas:

Can we Cure Indolent Lymphoma? clincancerres.aacrjournals.org  pdf 

The current consensus is that indolent lymphomas are incurable disorders. There are some indications that these malignancies are potentially curable. Indeed, not all indolent lymphomas are currently incurable. For example, patients with Ann Arbor stage I-Il indolent lymphomas can experience long-term disease-free survival and probable cure.
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Nabhan:

It Is Follicular... . So, Why CHOP?  jco.ascopubs.org/ 

" there has been much debate on what is the best front-line chemotherapy regimen to use in follicular and low-grade lymphomas, but no study to date has shown that the anthracycline-based approach is superior to nonanthracycline combinations."
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Czuczman:

Controversies in Follicular Lymphoma: "Who, What, When, Where, and Why?"  Hematology 2006:303-310. Full Text | PDF

In the current exciting era of targeted therapies (e.g., Rituxan, radioimmunoconjugates) and novel treatment approaches demonstrating an improvement in treatment outcomes (e.g., disease-free survival and OS), our old beliefs and historically accepted dogma need to be retested and revitalized. The optimal combination(s) of old and new agents and the optimal timing of when to initiate and how to sequence specific  therapies will require data from well-designed clinical trials that should include important correlative laboratory studies.
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Horning:

No consensus on frontline therapy for indolent nhl: 
Something Old, Something Few, Something Subjective, Something De´ ja` Vu  jco.org.PDF
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Meet the Professors - a provocative discussion among experts regarding first treatment options for advanced follicular lymphoma - meettheprofessors.com | PDF
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Webcast: Attacking NHL Early?   
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1984 Review: The natural history of initially untreated low-grade non-Hodgkin's lymphomas.  N Engl J Med. 1984 Dec 6; 311(23): 1471-5. PMID: 6548796 

Can we cure advanced indolent lymphomas?

Review articles, 
and Reports on 
single arm - non-comparative studies

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TOPIC SEARCH: PubMed

The Complete Response (CR) rate and durations of remissions (beyond 5 or 8 years?) suggests that an increasing fraction of patients with advanced indolent lymphomas may be cured.   However, more follow up is needed to say what fraction of patients may be cured --- but also in which clinical circumstances and with what protocols.  ~ KarlS

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Cabanillas: Can we Cure Indolent Lymphoma? clincancerres.aacrjournals.org  pdf 

The current consensus is that indolent lymphomas are incurable disorders. There are some indications that these malignancies are potentially curable. Indeed, not all indolent lymphomas are currently incurable. For example, patients with Ann Arbor stage I-Il indolent lymphomas can experience long-term disease-free survival and probable cure.
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Curability of Advanced Indolent or Low-Grade Follicular Lymphomas: Time for a New Paradigm? http://bit.ly/W8m8cR 

snip: "All these data tend to indicate that we have been assessing the
curability of indolent NHLs using criteria that specifically apply to
aggressive NHLs. In view of the different biology of these two disorders, it seems that we have been using the wrong criteria. I propose that when we evaluate the cure potential of a given treatment regimen for advanced low-grade follicular NHL, we should focus on more long-term follow-up data, particularly looking at FFS beyond 8 years."

 
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Each Subsequent [standard] Therapy Results in Diminishing Response Rate and Duration of  Response in Low Grade or Transformed Low Grade Non-Hodgkin's Lymphoma  ASCO 2001

"Evaluation of response and duration of response in these sixty patients to all prior chemotherapies  re-confirmed the previously published experience showing diminished response and duration of response with each subsequent chemotherapy.

In this same patient population the duration of response to the most recent chemotherapy was 4 months.  However, upon relapse, subsequent treatment with Bexxar (a type of RIT) provided a 10 month duration  of response (p=<0.001 ). An independent radiology and oncology review panel confirmed these findings. 

The high incidence of multiple relapses and the enduring decrease in both response and duration of response to subsequent therapy further reinforces the need for novel therapies for the treatment of LG  or Transformed LG NHL. New treatment options are necessary to provide greater clinical benefit  evidenced by both response and duration of response."
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Bexxar as initial treatment for follicular lymphoma.
N Engl J Med. 2005 Feb 3;352(5):441-9. Abstract | Full Text

After a median follow-up of 5.1 years,  the actuarial 5-year progression-free survival for all patients was  59 percent, with a median progression-free survival of 6.1 years. ...  

Of 57 (of 76) patients who had a complete response, 40 remained in remission for 4.3 to 7.7 years. Hematologic toxicity was moderate, with no patient requiring transfusions or hematopoietic growth factors. No cases of myelodysplastic syndrome have been observed.
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R-CHOP: Frontline therapy with rituximab added to the combination of CHOP significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005 Dec 1;106(12):3725-32. Epub 2005 Aug 25. PMID: 16123223  
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R-CHOP: Prolonged Clinical and Molecular Remission in Patients With Low-Grade or Follicular Non-Hodgkin's Lymphoma Treated With Rituximab Plus CHOP Chemotherapy: 9-Year Follow-Up  jco.org full text

Small study:  Overall response rate was 100%; 87% of patients achieved a complete response or unconfirmed complete response. The median TTP and DR were 82.3 months and 83.5 months, respectively. Seven of eight patients who were bcl-2 positive at baseline converted to negative, and three of the seven patients have sustained the molecular remission. 

CONCLUSION: Although a cure has not been found yet for follicular NHL, the R-CHOP combination provides a lengthy response duration in patients with relapsed or newly diagnosed indolent NHL.
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Bendandi: Aiming at a curative strategy for follicular lymphoma.
CA Cancer J Clin. 2008 Sep-Oct;58(5):305-17. Epub 2008 Aug 28.
PMID: 18755938 

"One clear fact is that no patients will ever be cured by adopting a palliative treatment approach. The assumption that patients with follicular lymphoma are incurable is certain to be a self-fulfilling prophecy. Here the author summarizes the large and growing body of knowledge that suggests an expectant approach to management is not appropriate for all patients.
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Combined therapy in advanced stages (III and IV) of follicular lymphoma increases the possibility of cure: results of a large controlled clinical trial. [in patients with nodal bulky disease] - Eur J Haematol 2002: 68: 144-149  PDF

Treatment Review Articles

Review article

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TOPIC SEARCH: PubMed | Systematic Reviews 

NHL, unspecified subtype

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A systematic overview of radiation therapy effects in non-Hodgkin's lymphoma. Acta Oncol. 2003;42(5-6):605-19.
Review. PMID: 14596518
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A systematic overview of chemotherapy effects in indolent non-Hodgkin's lymphoma. Acta Oncol. 2001;40(2-3):213-23.
Review. PMID: 11441933 abstract
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Autologous stem cell transplantation for malignancy: a systematic review of the literature. Clin Lab Haematol. 2000 Apr;22(2):61-72. Review. PMID: 10792394

Indolent lymphomas / CLL

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Each Subsequent Therapy Results in Diminishing Response Rate and Duration of Response in Low Grade or Transformed Low Grade Non-Hodgkin's Lymphoma.  ASCO 2001 Abstract 1165 
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Immunochemotherapy in indolent non-Hodgkin's lymphoma
Semin Oncol. 2002 Apr;29(2 Suppl 6):11-7. Review. PMID: 12040529 
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Should all patients with indolent lymphoma be treated with rituximab maintenance therapy? An overview of the data. Clin Lymphoma Myeloma. 2006 Oct;7 Suppl 1:S20-3. PMID: 17101069 | Related articles
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A systematic overview of chemotherapy effects in indolent non-Hodgkin's lymphoma. Acta Oncol. 2001;40(2-3):213-23.
Review. PMID: 11441933 
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Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. Drugs. 2003;63(8):803-43.
Review. PMID: 12662126
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A systematic overview of chemotherapy effects in B-cell chronic lymphocytic leukaemia. Acta Oncol. 2001;40(2-3):224-30.
Review. PMID: 11441934
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Non-Hodgkin's lymphoma: review of conventional treatments. Curr Pharm Biotechnol. 2001 Dec;2(4):279-91.
PMID: 11762410 abstract
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Role of anti-idiotype vaccines in the modern treatment of human follicular lymphoma.
Expert Rev Anticancer Ther. 2001 Jun;1(1):65-72.
Review. PMID: 12113135

Hodgkin's

  • A systematic overview of chemotherapy effects in Hodgkin's disease.
    Acta Oncol. 2001;40(2-3):185-97. Review. PMID: 11441931

MALT/Marginal Zone

  • Radiotherapy for extranodal, marginal zone, B-cell lymphoma of mucosa-associated lymphoid tissue originating in the ocular adnexa: a multiinstitutional, retrospective review of 50 patients. Cancer. 2003 Aug 15;98(4):865-71. PMID: 12910532  Pubmed | Related abstracts

Comparing Protocols 

Response & Response Duration & Survival  

Reports on 
dual arm - 
comparative studies,

 and comparisons of  outcomes for different protocols across studies

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TOPIC SEARCH: PubMed 
 
Currently Recruiting Randomized Lymphoma Studies: ClinicalTrials.gov 
an easy way to review treatments that
are considered most promising

Indolent Lymphomas
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Bendamustine Plus Rituximab Versus CHOP Plus Rituximab in the First-Line Treatment of Patients with Indolent and Mantle Cell Lymphomas First Interim Results of a Randomized Phase III Study of the StiL abstracts2view.com 

Results: So far 439 patients have been randomized. 273 patients are evaluable for response for this first interim analysis (B-R: n=139; CHOP-R: n=134). Median patient age is 63 years. Histologies are equally distributed between arms: follicular 52%, mantle cell 20%, and other indolent lymphomas 28% in both treatment groups, each. 

The ORR for pts treated with B-R was similar to that associated with CHOP-R (94% vs 93%, respectively). CR was also similar at 51% for B-R compared to 40% for CHOP-R. 

The median observation time for both groups is 17 months. Thus far, 15 deaths have been observed (B-R: 7; CHOP-R: 8). Progressive or relapsed disease has been documented during the follow-up period: 27 in pts treated with B-R and 32 in the CHOP-R group. 

The B-R regimen appears to have a better toxicity profile, as evidenced by a lower rate of total alopecia (40% CHOP-R vs. 0% with B-R) and a lower number of infectious complications (41 in CHOP-R pts vs. 19 in the B-R group).
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Role of Different Frontline Regimens in Achieving Complete Response in Follicular Lymphoma: A Meta-Analysis of CR Rate and Its Relation to Hazard Rate for Disease Progression. Session Type: Poster Session, Board #932-II  ASH2006 

"Random effect estimation showed a CRR of 
   37% with CHEMO (95% CI: 18%57%), 
   53% with RCHEMO (34%71%), 
   68% with FLU (49%87%), and 
   79% with RIT (73%85%) (fig 1).

The analysis suggests that a higher CRR is correlated with a lower hazard of disease progression. These data support the selection of regimens that achieve high CRRs for future trials of initial therapy and could provide an additional basis for the design of long-term therapeutic strategies."

CHEMO - chemotherapy combinations without fludarabine
R+/-CHEMO - rituximab as a single-agent or in combination with
   chemotherapy
FLU - fludarabine as a single-agent or in combination
RIT - Bexxar or Zevalin as  single agents or in combination
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High-Dose Sequential Chemotherapy with Rituxan® is Superior to CHOP-R for Poor Risk Follicular Lymphoma  cancerconsultants.com  

"Event-free survival at 40 months was approximately 65% for the high-dose group and 20% for the CHOP group. However, 83% of patients survived at 36 months in both arms. A stable molecular remission was achieved in 28% of R-CHOP patients and 78% of the high-dose group."
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CVP chemotherapy plus Rituximab compared with CVP as first-line treatment for advanced follicular lymphoma.  [322 patient study] 
Blood. 2004 Oct 19 PMID: 15494430 | Related articles | Full text
 
  Overall and complete response rates were 
  
        81% and 41% in the R-CVP arm vs.
        57% and 10% in the CVP arm, respectively (P < 0.0001).
 
    Median Time to progression: 32 months vs. 15 months for CVP; 
        (P < 0.0001).
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Randomized Phase III Study of Fludarabine Phosphate Versus Cyclophosphamide, Vincristine, and Prednisone (CVP) in Patients With Recurrent Low-Grade Non-Hodgkin's Lymphoma Previously Treated With an Alkylating Agent or Alkylator-Containing Regimen. J Clin Oncol. 2002 Dec 15;20(24):4649-54. PMID: 12488409  PubMed
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Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan (Zevalin) radioimmunotherapy versus rituximab (Rituxan)  immunotherapy for patients with relapsed or refractory low-grade, follicular, or  transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2002 May 15;20(10):2453-63. PMID: 12011122  PubMed
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Randomized controlled trial of Zevalin (yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy) versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or  transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2002 May 15;20(10):2453-63. PMID: 12011122  PubMed
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The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCMR) significantly increases the response rate and prolongs survival as compared to FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas - results of a prospective randomized study of the German low grade lymphoma study group (GLSG). Blood. 2004 Jul 29  PMID: 15284112 | Related abstracts | Full Text
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Standard chemotherapy with interferon compared to CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: the GELF-94 randomized study from the GELA. Blood. 2006 Jul 11  PMID: 16835383
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Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005 Dec 1;106(12):3725-32. Epub 2005 Aug 25.
PMID: 16123223
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Prolonged single-agent versus combination chemotherapy in indolent follicular lymphomas: a study of the cancer and leukemia group B. J Clin Oncol. 2003 Jan 1;21(1):5-15. PMID: 12506163  PubMed

"There is no advantage to the initial use of the relatively intensive combination, CHOP-B, for patients with Follicular small cleaved lymphoma compared with the less toxic single agent, cyclophosphamide. However, in an unplanned subgroup analysis, patients with Follicular mixed cell lymphoma  who received the combination experienced improved disease control and survival."
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Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival [Compared to consolidation with INF] in follicular lymphoma: results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group  bloodjournal.org Oct 2004  Commentary 
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High-dose CEB vs BEAM with autologous stem cell transplant in lymphoma. Bone Marrow Transplant. 2004 Jul 26 PMID: 15273714 | Related abstracts
Diffuse Large B-cell & Aggressive Lymphomas
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R-CHOP-14 in patients with diffuse large B-cell lymphoma younger than 70 years:  a multicentre, prospective study  ASCO 

After therapy, 58 patients (73%) achieved CR-CRu (95% CI: 55-90%). With a median follow-up of 26 months, progression-free survival (PFS) and overall survival (OS) at 30 months were 72% and 86%, respectively. Administration of R-CHOP-14 is feasible and effective in patients <70 years.
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CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42.
PMID: 11807147 PubMed

 

 Rituxan 
as single agent

Reports on 
single arm - non-comparative studies
or comparisons of same agent with different treatment schedule

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TOPIC SEARCH: PubMed 

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Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. PMID: 14976046 

In 185 evaluable patients, the overall response rate was: 
   67% in chemotherapy-naive patients and 
   46% in pretreated cases (P <.01). 

Patients responding or with stable disease at week 12 (n = 151) were randomized to no further treatment or prolonged rituximab administration (375 mg/m(2) every 2 months for 4 times). At a median follow-up of 35 months, the median event-free survival (EFS) was: 
   12 months in the no further treatment versus 
   23 months in the prolonged treatment arm (P =.02), 

the difference being particularly notable in chemotherapy-naive patients 
  (19 vs 36 months; P =.009) and in patients responding to induction
  treatment  (16 vs 36 months; P =.004). 

The number of t(14;18)-positive cells in peripheral blood (P =.0035) and in bone marrow (P =.0052) at baseline was predictive for clinical response.
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Should all patients with indolent lymphoma be treated with rituximab maintenance therapy? An overview of the data. Clin Lymphoma Myeloma. 2006 Oct;7 Suppl 1:S20-3. PMID: 17101069 | Related articles
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Also see Rituxan abstracts

Chemo-Rituxan-based protocols

(without Fludarabine)

Reports on 
single arm - non-comparative studies,
or comparisons of same agent with different treatment schedules

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TOPIC SEARCH: Chemotherapy and Rituxan PubMed

Currently Recruiting Randomized Lymphoma Studies: ClinicalTrials.gov 

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Combined cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) improves response rates but not survival and has lower hematologic toxicity compared with combined mitoxantrone, chlorambucil, and prednisone (MCP) in follicular and mantle cell lymphomas: results of a prospective randomized trial of the German Low-Grade Lymphoma Study Group. Cancer. 2006 Jul 28;  PMID: 16878325 

"Taking into account that, currently, chemotherapy regularly is combined with rituximab as first-line therapy for FL and MCL, the data from this study may have an impact on the type of chemotherapy to be applied in such combinations. Particularly in younger, high-risk patients who are candidates for autologous stem cell transplantation, CHOP should be preferred over MCP."
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Prolonged Clinical and Molecular Remission in Patients With Low-Grade or Follicular Non-Hodgkin's Lymphoma Treated With Rituximab Plus CHOP Chemotherapy: 9-Year Follow-Up. J Clin Oncol. 2004 Oct 13, Czuczman  PMID: 15483015 | Related articles  | Medscape 
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The role of anthracyclines in combination chemotherapy for the treatment of follicular lymphoma: retrospective study of the Intergruppo Italiano Linfomi on 761 cases. Leuk Lymphoma. 2003 Nov; 44(11): 1911-7. PMID: 14738142 | Related articles
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[1493] Patients with Low-Grade NHL Treated with Rituximab + CHOP Experience Prolonged Clinical and Molecular Remission. Session Type: Poster Session 605-I ~ Myron Czuczman et al ASH 2003
  • Update: Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin’s lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol 2004;22(23):4711-6. Abstract
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Phase II study of rituximab in combination with CHOP chemotherapy in patients with previously untreated, aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2001 Jan 15;19(2):389-97. PMID: 11208830  PubMed
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Rituximab (anti-CD20 monoclonal antibody) as consolidation of first-line CHOP chemotherapy in patients with follicular lymphoma: a phase II study.
Eur J Haematol. 2002 Jul;69(1):21-6. PMID: 12270058   PubMed
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Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue. An uncontrolled trial. Ann Intern Med. 1999 Jul 20;131(2):88-95. PMID: 10419446  | Full text
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Clinical Implications of Antibody Mechanisms of Action  Medscape (free login req.)
 
"The Groupe d'Etudes des Lymphomes de l'Adulte group compared CHOP with rituximab/CHOP in a group of 399 elderly patients ranging from 60 to 80 years of age with diffuse large B-cell NHL.[22] Administered in the same fashion as described in the Vose study above, the following results were observed at a median follow-up of 2 years (Table 2)."

Table 2.
CHOP Vs CHOP/Rituximab in Elderly Patients With Diffuse Large B-Cell NHL: A GELA Study

Regimen CR/CRu PR Progression Treatment-Related Death Rate
CHOP 62% 6% 21% 7%
CHOP/rituximab 76% 6% 9% 5%

CHOP, cyclophosphamide, doxorubicin, vincristine, prednisone; NHL, non-Hodgkin's lymphoma; GELA, Groupe d'Etudes des Lymphomes de l'Adulte; CR, complete response; CRu, unconfirmed complete response; PR, partial response

Fludarabine-Rituxan-based protocols

Reports on 
single arm - non-comparative studies, or comparisons of same agent with different treatment schedule

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TOPIC SEARCH: CHOP+ Rituxan PubMed

Currently Recruiting Randomized Lymphoma Studies: ClinicalTrials.gov 

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Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma. J Clin Oncol. 2005 Feb 1;23(4):694-704. PMID:15681517 

An overall response rate of 90% (80% complete response rate) was achieved in the intent-to-treat population. Similar response rates were seen in treatment-naive and previously treated patients. The median duration of response has not been reached at 40+ months. The median follow-up time in this study is 44 months (range, 15 to 66 months). In patients positive for the 14;18 translocation in blood and/or marrow at enrollment, molecular remission was achieved in 88% of cases, with patients remaining negative for up to 4 years to date. Hematologic toxicity was manageable, and except for a 15% incidence of herpes simplex/zoster infections, infectious complications were rare. Nonhematologic toxicities were minimal.
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Phase 2 study of a combined immunochemotherapy using rituximab and fludarabine in patients with chronic lymphocytic leukemia. Blood. 2002 Nov 1;100(9):3115-20. PMID: 12384407  PubMed
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Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712). Blood. 2003 Jan 1;101(1):6-14. PMID: 12393429  PubMed
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Stage IV indolent lymphoma: A randomized study of concurrent vs. sequential use of FND chemotherapy (fludarabine, mitoxantrone, dexamethasone) and rituximab (R) monoclonal antibody therapy, with interferon maintenance  ASCO 2003
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Increased response rate with rituximab in relapsed and refractory follicular and mantle cell lymphomas -- results of a prospective randomized study of the German Low-Grade Lymphoma Study Group Dtsch Med Wochenschr. 2002 Oct 25;127(43):2253-8. German.
PMID: 12397539  PubMed 
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Dramatic efficacy of fludarabine in the treatment of an aggressive case of splenic lymphoma with villous lymphocytes. Eur J Haematol. 2002 Aug;69(2):112-4. PMID: 12366716  PubMed 

Immune suppression and Fludarabine

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Decrease of CD-4 cells and CD-8 cells - Includes a summary on the toxicities Associated with Purine Analog Therapy by  Bruce D. Cheson   oikos.org
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Eosinophilic pneumonia after administration of fludarabine for the treatment of non-Hodgkin's lymphoma. Ann Hematol. 2002 Sep;81(9):535-7. PMID: 12373357  PubMed
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Epstein-Barr virus-positive B-cell lymphoproliferative disorders arising in immunodeficient patients previously treated with fludarabine for low-grade B-cell neoplasms. Am J Surg Pathol. 2002 May;26(5):630-6. PMID: 11979093  PubMed

Stem cell-based

Reports on 
single arm - non-comparative studies

 

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TOPIC SEARCH: PubMed

Currently Recruiting Randomized Lymphoma Studies: ClinicalTrials.gov 

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Allogeneic stem cell transplantation in follicular lymphoma: recent progress and controversy http://bit.ly/9QY8aa

"Allogeneic stem cell transplantation (allo HCT) is a curative treatment for follicular lymphoma, but is hampered by a relatively high treatment-related mortality and by difficulties in identifying high-risk groups for whom transplant is warranted."
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High-dose CEB vs BEAM with autologous stem cell transplant in lymphoma.Bone Marrow Transplant. 2004 Jul 26 PMID: 15273714 | Related abstracts
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Myeloablative radio-chemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma - results of a prospective randomized trial of the German Low-Grade Lymphoma Study Group (GLSG). Blood. 2004 Jul PMID: 15238420
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Long-term disease-free survival of patients with advanced follicular lymphoma after allogeneic bone marrow transplantation. Br J Haematol. 2004 Nov;127(3):311-21. PMID: 15491292 | Related articles
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Favourable Overall Survival with Myeloablative Allogeneic Stem Cell Transplantation for Follicular Lymphoma  ASH 2006 

The five year overall survival is 77% (95% confidence intervals 73  91%) with a median follow-up of 48 months post-SCT.

Treatment-related mortality was 5 of 41 pts (12%).

Non-relapse mortality was seen in one patient (3%).

One patient has relapsed at over 3 years post-SCT while all recipients of syngeneic SCT remain in remission.
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Allogeneic hematopoietic stem cell transplantation for progressive follicular lymphoma.  Bone Marrow Transplant. 2002 Jun;29(12):973-8. PMID: 12098065  PubMed
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Allogeneic stem-cell transplantation for lymphoproliferative disorders using BEAM-CAMPATH (+/- fludarabine) conditioning combined with post-transplant donor-lymphocyte infusion. Cytotherapy. 2001;3(3):203-10. 
PMID: 12171727  PubMed
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High-dose therapy with autologous bone marrow support as consolidation of remission in follicular lymphoma: long-term clinical and molecular follow-up. J Clin Oncol. 2000 Feb;18(3):527-36. PMID: 10653868 PubMed abstract
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Long-term survival of patients with resistant lymphoma treated with tandem stem cell transplant. Leuk Lymphoma. 2005 Mar;46(3):405-14. PMID: 15621831 | Related articles
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Stem cell transplantation in follicular lymphoma: progress at last?
Bone Marrow Transplant. 2004 Oct 18 PMID: 15489883 | Related articles 
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Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival [Compared to consolidation with INF] in follicular lymphoma: results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group  bloodjournal.org Oct 2004  Commentary 

T-cell, peripheral type

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Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation.
Leukemia. 2006 Sep;20(9):1533-8. Epub 2006 Jul 27. PMID: 16871285 

... our findings indicate (1) up-front high-dose therapy and ASCT are feasible, but could induce a high rate of long-term CR only in patients with ALK-positive ALCL and (2) the achievement of CR before autografting is a strong predictor of better survival."

Radiotherapy

Localized | Advanced

Reports on 
single arm - non-comparative studies

 

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TOPIC SEARCH: 
 
Currently Recruiting Randomized Lymphoma Studies: ClinicalTrials.gov 

Localized lymphoma:
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Long-term outcome and mortality trends in early-stage, Grade 1-2 follicular lymphoma treated with radiation therapy. Int J Radiat Oncol Biol Phys. 2006 Mar 1;64(3):928-34. Epub 2005 Oct 21. PMID: 16243446 

RESULTS: Median follow-up was 12 years. Median survival time was 19 years. The 5-, 10-, and 15-year overall survival (OS) rates were 93%, 75%, and 62%, respectively. Age > or = 60 was the only significant adverse prognostic factor with respect to OS. There were 35 deaths, 20 of which were attributable to lymphoma. Freedom from treatment failure (FFTF) rates at 5, 10, and 15 years were 72%, 46%, and 39%, respectively. Forty-seven patients (48%) relapsed. Tumor size > 3 cm was the only significant adverse factor for FFTF. Observed incidence of second malignancy did not significantly exceed expected incidence.
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Long-term results with radiotherapy for Stage I-II follicular lymphomas.
Int J Radiat Oncol Biol Phys. 2001 Dec 1;51(5):1219-27. PMID: 11728680 - PubMed
CONCLUSIONS: RT can cure approximately one half of Stage I and one quarter of Stage II, World Health Organization Grade 1 or 2 follicular lymphomas. Follicular lymphomas <3.0 cm can be controlled locally with doses of 27.8-30.8 Gy, and there is a trend toward a higher incidence of late complications with doses of >30.8 Gy. Doses of 25-30 Gy delivered in 15-20 fractions should be examined prospectively in patients with follicular lymphomas of <3.0 cm.
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Is radiotherapy curative for stage I and II low-grade follicular lymphoma? Results of a long-term follow-up study of patients treated at Stanford University  www.jco.org
Advanced Lymphoma
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Adjuvant radiotherapy [to sites of bulky disease] in stage IV diffuse large cell lymphoma improve outcome. Leuk Lymphoma. 2004 Jul;45(7):1385-9. PMID: 15359637 | Related articles
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Long-term results with radiotherapy for Stage I-II follicular lymphomas.
Int J Radiat Oncol Biol Phys. 2001 Dec 1;51(5):1219-27. PMID: 11728680 - PubMed
CONCLUSIONS: RT can cure approximately one half of Stage I and one quarter of Stage II, World Health Organization Grade 1 or 2 follicular lymphomas. Follicular lymphomas <3.0 cm can be controlled locally with doses of 27.8-30.8 Gy, and there is a trend toward a higher incidence of late complications with doses of >30.8 Gy. Doses of 25-30 Gy delivered in 15-20 fractions should be examined prospectively in patients with follicular lymphomas of <3.0 cm.
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Salvage central lymphatic irradiation in follicular lymphomas following failure of chemotherapy: a feasibility study.
CONCLUSIONS: These results demonstrate for the first time that with CLI, it is possible to achieve complete remission of acceptable quality in follicular lymphoma patients who experience a chemotherapy failure. The main toxicity is limited to transient depression in hematological profiles. The treatment is fairly well tolerated and seems to carry little risk compared with high-dose chemotherapy and bone marrow rescue. Salvage CLI may not necessarily compromise future treatment with chemotherapy, including autologous bone marrow or stem cell transplantation, because the patients' blood counts recover.
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Central lymphatic irradiation for stage III nodular malignant lymphoma: long-term results.  
 
CONCLUSION: These results suggest that initial comprehensive central lymphatic irradiation may be the preferred approach to achieve a durable relapse-free interval for this group of patients
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Comprehensive lymphatic irradiation for stage II-III non-Hodgkin's lymphoma.  
 
This approach has been well tolerated and has produced relapse-free and overall survival rates at 10 years of 60 and 66%, respectively.
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Is comprehensive lymphatic irradiation for low-grade non-Hodgkin's lymphoma curative therapy? Long-term experience at a single institution. Int J Radiat Oncol Biol Phys. 1997 Apr 1;38(1):3-8.
PMID: 9211997  PubMed  
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Primary Radiotherapy May Benefit Stage III Follicular Lymphoma Patients 
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Long-term follow-up of patients with Stage III follicular lymphoma treated with primary radiotherapy at Stanford University. Int J Radiat Oncol Biol Phys. 2001 Jan 1;49(1):3-15. Erratum in: Int J Radiat Oncol Biol Phys 2001 May 1;50(1):285.
PMID: 11163492
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Long-term outcome after radiotherapy alone for lymphocyte-predominant Hodgkin lymphoma. Cancer. 2005 Aug 10; PMID: 16094666

(RIT) 
 
Radio-Immunotherapy-
based protocols 

Bexxar | Zevalin

Reports on 
single arm - non-comparative studies

 

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Bexxar (Iodine-131 Tositumomab)

TOPIC SEARCH: Bexxar-based protocols
Currently Recruiting Randomized Lymphoma Studies: ClinicalTrials.gov 

Bexxar

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Phase II trial of CHOP chemotherapy followed by Bexxar for previously untreated follicular non-Hodgkin's lymphoma: five-year follow-up of Southwest Oncology Group Protocol S9911. J Clin Oncol. 2006 Sep 1;24(25):4143-9. Epub 2006 Aug 8. PMID: 16896003
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New treatment, CHOP followed by Bexxar, shows long-term remission in patients with follicular non-Hodgkin’s lymphoma  bexxar s0016.pdf

“We feel that the five-year results of the trial are tremendously encouraging and some of the best ever observed in a SWOG clinical trial for patients with advanced follicular non-Hodgkin’s lymphoma,” said Dr. Press, who is a member of the Fred Hutchinson Cancer Research Center, professor of medicine at the University of Washington and chairman of the scientific advisory board of the Lymphoma Research Foundation.
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 [Bexxar] in Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma: Australian Multicenter Phase II Clinical Study. J Clin Oncol. 2006 Aug 28; PMID: 16940276 

The objective overall response rate (ORR) was 76%, with 53% attaining a complete response (CR) or CR unconfirmed (CRu). Median duration of response for patients achieving CR/CRu was 20 v 7 months for those with a partial response (P = .0121). Median progression-free survival for the entire cohort was 13 months, with 14% remaining relapse free beyond 4 years. Median follow-up was 23 months, with a 4-year actuarial survival rate of 59% +/- 10%. Toxicity was principally hematologic; grade 4 thrombocytopenia occurred in 4% and neutropenia occurred in 16% of patients, with nadirs at 6 to 7 weeks after treatment. 
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Bexxar Following Fludarabine Produced Response in 100% of patients [first line]  med.cornell.edu  Sep 2005
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Radioactive Anti-CD 20 Antibody (Bexxar®) May Improve Outcome of Autologous Transplants for Follicular Lymphomas  cancerconsultants.com 
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Efficacy and Safety of Tositumomab and Iodine-131 Tositumomab (Bexxar) in B-Cell Lymphoma, Progressive After Rituximab. J Clin Oncol. 2004 Dec 21;  PMID: 15613695
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Tositumomab and Iodine I 131 Tositumomab [Bexxar] for Recurrent Indolent and Transformed B-Cell Non-Hodgkin's Lymphoma. J Clin Oncol. 2004 Apr 15;22(8):1469-79. PMID: 15084620 | Related articles
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ASH 2003 - [89] The Bexxar Therapeutic Regimen (Tositumomab and Iodine I 131 Tositumomab) Produced Durable Complete Remissions in Heavily Pretreated Patients with Non-Hodgkins Lymphoma (NHL), Rituximab-Relapsed/Refractory Disease, and Rituximab-Naive Disease.  abstractsview.com


Zevalin (Yttrium-90 Ibritumomab Tiuxetan)

TOPIC SEARCH: Zevalin-based protocols
Currently Recruiting Randomized Lymphoma Studies: ClinicalTrials.gov 
an easy way to review treatments that
are considered most promising)

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Follow-up results of a phase II study of ibritumomab tiuxetan radioimmunotherapy in patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma and mild thrombocytopenia. Cancer Biother Radiopharm. 2004 Aug;19(4):478-81. PMID: 15453962
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ASCO 2003 - Report on Zevalin - durable responses; safety as second- or third-line therapy  Buswire
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4-year data: Safety of Yttrium-90 Ibritumomab Tiuxetan Radioimmunotherapy for Relapsed Low-Grade, Follicular, or Transformed Non-Hodgkin's Lymphoma. J Clin Oncol. 2003 Apr 1;21(7):1263-70. PMID: 12663713  PubMed
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Durable Remissions Obtained with Zevalin in Recurrent Follicular Lymphoma  CancerConsultants.com 

Vaccine-based

Reports on 
single arm - non-comparative studies, or comparisons of same protocol with different treatment schedule

 

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TOPIC SEARCH: PubMed

Currently Recruiting Randomized Lymphoma Studies: ClinicalTrials.gov 

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BiovaxID™ Vaccine Therapy of Follicular Lymphoma in First Remission: Long-Term Follow-Up of a Phase II Trial and Status of a Controlled, Randomized Phase III Trial. Session Type: Poster Session 645-II 
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ASH 2003 Update: Cellular Therapies and Vaccines 
for Hematologic Malignancies  CancerConsultants.com
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Induction of T-cell responses by tumor antigen vaccination in mantle cell lymphoma following rituximab-based treatment  ASCO 2003
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Clinical Outcome of Lymphoma Patients After Idiotype Vaccination Is Correlated With Humoral Immune Response and Immunoglobulin G Fc Receptor Genotype.
J Clin Oncol. 2004 Oct 13 PMID: 15483014 |
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Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma. Nat Med. 1999 Oct;5(10):1171-7. PMID: 10502821PDF | PDF-Help
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Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients. Blood. 2002 Mar 1;99(5):1517-26. PMID: 11861263 PubMed
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Idiotype vaccination following ABMT can stimulate specific anti-idiotype immune responses in patients with B-cell lymphoma. Biol Blood Marrow Transplant. 2001;7(9):517-22. PMID: 11669219  PubMed
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Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma -- long-term results of a clinical trial. Blood. 1997 May 1;89(9):3129-35. PMID: 9129015 
Hsu FJ, Caspar ... Levy R. | PDF | PDF-Help | Abstracts 
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Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med. 1996 Jan;2(1):52-8. PMID: 8564842; UI: 96135165.  Hsu FJ, et al.  See Related Articles
Type
Resource
Indolent CLL | Follicular | MALTT-cell 
Aggressive DLBCL | T-cell
Hodgkins ... under construction
Other
  • High dose cyclophosphamide plus recombinant human granulocyte-colony stimulating factor (rhG-CSF) in the treatment of follicular, low grade non-Hodgkin's lymphoma: CALGB 9150. Leuk Lymphoma. 2001 Nov-Dec;42(6):1255-64.
    PMID: 11911406
 
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