Abstracts reporting on t-cell lymphomas at ASH 2010
Pralatrexate Is Effective In Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma (PTCL) with Prior Ifosfamide, Carboplatin, and Etoposide (ICE)-Based Regimens http://ash.confex.com/ash/2010/webprogram/Paper28321.html
Conclusions Pralatrexate was highly active in patients with PTCL who received prior ICE-based chemotherapy, with an ORR of 40% including CRs leading to SCT in some patients. Of note, is the long duration of pralatrexate responses in marked contrast to the short response duration of the combination chemotherapy regimens. Taken together, the efficacy of single-agent pralatrexate compared favorably with ICE-based regimens, a finding that is consistent with other exploratory analyses, showing that pralatrexate can reverse the characteristic progressive resistance of PTCL patients to second-line chemotherapy, and that pralatrexate is an effective second-line treatment for patients with PTCL.
Final Results From a Pivotal, Multicenter, International, Open-Label, Phase 2 Study of Romidepsin In Progressive or Relapsed Peripheral T-Cell Lymphoma (PTCL) Following Prior Systemic Therapy http://ash.confex.com/ash/2010/webprogram/Paper30063.html
Conclusions: Complete and durable responses were observed with single agent romidepsin in pts with relapsed PTCL. These data support the therapeutic potential for romidepsin in relapsed PTCL and suggest that romidepsin is a strong candidate for inclusion in future novel regimens for these diseases.
Multicenter Phase II Study of KW-0761, a Defucosylated Anti-CCR4 Antibody, In Relapsed Patients with Adult T-Cell Leukemia-Lymphoma (ATL) http://ash.confex.com/ash/2010/webprogram/Paper29172.html
Conclusions: KW-0761 is a highly effective agent with acceptable toxicity profiles in relapsed patients with CCR4-positive ATL who have no standard therapies. A multicenter, randomized study for untreated ATL patients to compare mLSG15 (a dose-intensified multi-agent regimen, J Clin Oncol 2007;25:5458-64) + KW-0761 with mLSG15 alone has been initiated.
Interim Results of a Phase 1 Trial of An Oral Histone Deacetylase Inhibitor Belinostat In Patients with Lymphoid Malignancies (b or t-cell) http://ash.confex.com/ash/2010/webprogram/Paper33728.html
Conclusions: Oral Bel can be administered safely with a d 1-14, q3w schedule in pts with lymphoma at a daily dose higher than what has been established for pts with solid tumors. Protocol defined DLTs have been encountered in the dose range 750 – 2000mg in pts with lymphoma. Cohort D at 1500 mg was expanded due to 1 DLT (diarrhea). Cohort E at 1750 mg was tolerated without DLT and cohort F 2000 mg is currently being investigated. Final evaluation will include additional pts and possible dose escalation. The safety profile and early tumor shrinkage noted in MCL and HD warrants continued evaluation of Bel, especially in combination with other active compounds.
Identification of An Active, Well-Tolerated Dose of Pralatrexate In Patients with Relapsed or Refractory Cutaneous T-Cell Lymphoma (CTCL): Final Results of a Multicenter Dose-Finding Study http://ash.confex.com/ash/2010/webprogram/Paper28381.html
Conclusions: Pralatrexate shows high activity with acceptable toxicity in patients with relapsed or refractory CTCL at the identified optimal dose and schedule of 15 mg/m2 weekly for 3/4 weeks. The lack of significant hematologic toxicity or cumulative toxicity seen in this study suggests that pralatrexate should be further evaluated as continuous or maintenance therapy for patients with CTCL. Final efficacy and tolerability data will be reported.
The Prognosis of Limited Stage Peripheral T-Cell Lymphoma (PTCL): A Population-Based Analysis and Comparison to Diffuse Large B-Cell Lymphoma (DLBCL) http://ash.confex.com/ash/2010/webprogram/Paper27282.html
Conclusion: Limited stage cutaneous-only PTCL-NOS and ALK-pos ALCL as well as selected patients with PTCL-NOS and ALK-neg ALCL with low risk disease have a favourable prognosis. However, the prognosis remains inferior to limited stage DLBCL. Despite an overall higher risk of relapse, the cure rate is high in limited stage PTCL patients who are able to receive a stem cell transplant as part of their salvage therapy for relapsed or refractory disease.
Intensive Induction Chemotherapy Followed by Autologous Stem Cell Transplantation (ASCT) In Patients with Enteropathy-Associated T-Cell Lymphoma: a Prospective Study by the Nordic Lymphoma Group (NLG-T-01) http://ash.confex.com/ash/2010/webprogram/Paper27924.html
In this prospective study, intensive induction chemotherapy followed by ASCT was feasible in the majority of younger patients with EATL. In a subset of patients, who should clinically and biologically be further characterized, long-term outcome seems promising when compared to historical controls. Whether addition of other chemotherapeutic agents, antibodies such as alemtuzumab or other biologicals may further improve long-term outcome remains to be studied.
The Novel Organic Arsenical, Darinaparsin (ZIO-101), Induces Apoptosis through AKT and MEK/ERK Pathways In Hodgkin Lymphoma (HL) and T-Cell Lymphoma (TCL) Cell Lines http://ash.confex.com/ash/2010/webprogram/Paper32058.html
Conclusions: Darninaparsin induces significant cell death in HL and TCL cell lines that is mediated through AKT and MEK/ERK-based pathways. Additionally, markedly higher intracellular darinaparsin levels are achieved in lymphoma cells compared with equivalent concentrations of ATO. Continued pre-clinical and clinical trial investigation of darinaparsin in HL and TCL is warranted.
A Retrospective Analysis on Prognostic Factors of Angioimmunoblastic T-Cell Lymphoma: a Multicenter Cooperative Study In Japan http://ash.confex.com/ash/2010/webprogram/Paper31134.html
[Conclusion] Prognosis of patients with AITL in Japan is poor. Although IPI was useful in prognostification of AITL, other factors including those not adopted in IPI, such as IgA, anemia, TP and CRP, significantly affected the prognosis in this analysis. Further validation studies of these criteria should be performed.
Efficacy of Denileukin Diftitox Retreatment In Patients with Cutaneous T-Cell Lymphoma Who Relapsed After Initial Response http://ash.confex.com/ash/2010/webprogram/Paper31796.html
Conclusion: Patients with CD25-positive CTCL who had been treated previously with DD and subsequently relapsed were able to show durable responses upon retreatment. The observed ORR of 40% was similar to that seen with primary treatment with an estimated median duration of response of 9.8 months.
Outcomes In Allogeneic Hematopoietic Stem Cell Transplantation for Peripheral T-Cell Lymphoma: A Single Center's 12-Year Experience http://ash.confex.com/ash/2010/webprogram/Paper31994.html
We conclude that allogeneic HSCT can provide durable remission and survival for patients with relapsed and refractory PTCL, with acceptable treatment-related mortality. Future prospective trials are needed to further define the role of allogeneic HSCT in this patient population.
The Combination of Histone Deacetylase Inhibitors and Hypomethylating Agents Exhibits Marked Synergy In Preclinical Models of T-Cell Lymphoma http://ash.confex.com/ash/2010/webprogram/Paper31322.html
Collectively, the data suggest that the combination of a hypomethylating agent like D and a HDACI (B and R) are synergistic in in vitro models of human T-cell lymphoma, and may lead to a new platform for the treatment of these diseases.
Favorable Outcome In ALK-Negative Anaplastic Large-Cell Lymphoma Following Intensive Induction Chemotherapy and Autologous Stem Cell Transplantation (ASCT): a Prospective Study by the Nordic Lymphoma Group (NLG-T-01) http://ash.confex.com/ash/2010/webprogram/Paper27948.html
In ASCT eligible patients, intensive induction chemotherapy consolidated by upfront ASCT is an effective treatment that yields outcome results at least as good as those obtained in age-comparable patients with diffuse large B-cell lymphoma.
Multicenter Phase II Study of the CyclOBEAP Regimen for Patients with Peripheral T-Cell Lymphoma with Analysis of Biomakers http://ash.confex.com/ash/2010/webprogram/Paper27395.html
Our results suggest that the CyclOBEAP therapy is safe and effective for the treatment of PTCLs. Furthermore, nm23-H1 protein expression may be an important prognostic factor in PTCLs.
Aplidin® (Plitidepsin) Activity In Peripheral T-Cell Lymphoma (PTCL): Final Results http://ash.confex.com/ash/2010/webprogram/Paper29970.html
Conclusions Plitidepsin has activity, with an acceptable safety profile in non-cutaneous relapsed/refractory PTCL patients. Remarkably, lack of hematologic toxicity makes plitidepsin an ideal agent either for treating patients with poor bone marrow reserve or combining it with other active agents. A combination of plitidepsin with gemcitabine is currently being explored in this patient population.
Low Absolute Lymphocyte Count Predicts Chemotherapy Response and Survival In Peripheral T-Cell Lymphoma, NOS http://ash.confex.com/ash/2010/webprogram/Paper34796.html
This study suggested that low ALC is an independent prognostic factor for survival in patients with PTCL, NOS.
Addition of Anti-Viral Therapy to Chemotherapy Improves Overall Survival In Acute and Lymphomatous Adult T-Cell Leukaemia/Lymphoma (ATLL) http://ash.confex.com/ash/2010/webprogram/Paper33893.html
Conclusions Our results point to the benefit of treatment with ZDV/IFN at some stage, given the failure of any patient to survive 2 years in the absence of this therapy. In the recent meta-analysis insufficient patient numbers with lymphoma were treated with adjunctive ZDV/IFN therapy to demonstrate any benefit, whilst first line therapy with ZDV/IFN alone was ineffective. However, we have documented significant clinical benefit from the addition of ZDV/IFN to chemotherapy in lymphomatous ATLL. Together these two studies suggest the following treatment approach to improve outcome in aggressive ATLL: Acute type– 1st line treatment with AZT/IFN alone. Lymphomatous type - 1st line treatment with chemotherapy and early addition of ZDV/IFN. This is a major step forward in ATLL therapy, but it is important to recognise that some patients will fail therapy and overall survival remains poor.
Smouldering Adult T-Cell Leukaemia/Lymphoma (ATLL) Is Not Associated with An Increased Risk of Aggressive ATLL In HTLV-1 Positive Patients http://ash.confex.com/ash/2010/webprogram/Paper33261.html
In this cohort fulfilment of the Shimoyama classification for smouldering ATLL was not associated with an increased risk of developing aggressive ATLL (1/43 v 2/107) during a median of 3.7 years of follow up. We therefore propose that ATLL should not be diagnosed in the absence of a raised lymphocyte count and/or organ involvement. However HTLV-1 proviral load does appear to be an important predictor for risk of ATLL and further study to identify patients at risk prior to development of this aggressive malignancy is warranted.
Enteropathy-Associated T-Cell Lymphoma: a Clinical Prognostic Model to Identify High Risk Patients http://ash.confex.com/ash/2010/webprogram/Paper27032.html
In conclusion, our new prognostic model clearly identifies a high and a low risk group. Patients with one or more of the risk factors serum LDH > normal, B-symptoms or subtype secondary EATL are at high risk, and therefore new therapies for this group are urgently needed.
Concurrent Chemo-Radiotherapy Followed by VIDL (Etoposide, Ifosfamide, Dexamethasone, L-asparaginase) Chemotherapy In Stage I/II Extranodal NK/T-Cell Lymphoma of Nasal Cavity/Nasopharynx http://ash.confex.com/ash/2010/webprogram/Paper29701.html
Concurrent chemo-radiotherapy followed by VIDL chemotherapy can be an effective treatment strategy with acceptable toxicity in stage I/II extranodal NK/T-Cell lymphoma of nasal cavity/nasopharynx.
Sufficient and Timely Autologous Stem Cell Harvest After Chemoimmunotherapy with Alemtuzumab In Combination with Bi-Weekly CHOP as First Line Treatment In Systemic Peripheral T-Cell Lymphomas (PTCL): a Feasibility Analysis From the First Randomized Trial In Systemic PTCL (ACT trial) http://ash.confex.com/ash/2010/webprogram/Paper31012.html
In conclusion, the addition of alemtuzumab to bi-weekly CHOP in the setting of first-line therapy of primary systemic PTCL does not significantly impair ASCH (autologous stem cell harvest ) prior to upfront autologous stem cell transplant.
Long-Term Outcome for De Novo Lymphoblastic Lymphoma (LL) After Frontline Therapy with Hyper-CVAD Regimen and Variants http://ash.confex.com/ash/2010/webprogram/Paper33894.html
An augmented hyper-CVAD regimen (dose intensifying VCR/dexamethasone components and incorporating pegylated asparaginase) has been successfully piloted in the salvage setting. The optimal first line chemotherapy of LL continues to be refined; the role of autologous or allogeneic SCT for LL in first CR remains unclear since majority of patients can be cured without use of these modalities.
Multicenter Phase II Study of KW-0761, a Defucosylated Anti-CCR4 Antibody, In Relapsed Patients with Adult T-Cell Leukemia-Lymphoma (ATL) http://ash.confex.com/ash/2010/webprogram/Paper29172.html
Conclusions: KW-0761 is a highly effective agent with acceptable toxicity profiles in relapsed patients with CCR4-positive ATL who have no standard therapies. A multicenter, randomized study for untreated ATL patients to compare mLSG15 (a dose-intensified multi-agent regimen, J Clin Oncol 2007;25:5458-64) + KW-0761 with mLSG15 alone has been initiated.
Gemcitabine, Ifosfamide, Oxaliplatin (GIFOX) as First-Line Treatment In High-Risk Peripheral T-Cell/NK Lymphomas: A Phase II Trial http://ash.confex.com/ash/2010/webprogram/Paper33733.html
Conclusions: GIFOX retains an attractive therapeutic potential as upfront strategy in PTCL, enabling cytoreduction and SCs mobilization for ASCT consolidation, and allows the safe delivery of a full induction program also to patients aged or unfit for high dose therapy.
Response Rate of 16% and High Incidence of Adverse Events In Placebo-Treated Patients with CD25 Assay-Positive Cutaneous T-Cell Lymphoma (CTCL): An Analysis of Patient Characteristics and Predictors of Response http://ash.confex.com/ash/2010/webprogram/Paper32102.html
Conclusion: The findings from this study demonstrate that responses can be observed in patients with MF/SS in the absence of anti-tumor treatment. Likely contributing factors to these ‘spontaneous responses’ are the use of systemic antibiotics, aggressive ‘rescue medication’ use and the waxing and waning nature of skin lesions, particularly in early-stage disease. All future studies should carefully document the use of systemic antibiotics during therapy. These results can serve as standard comparators for other active-treatment studies that lack a placebo control arm.
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