ASH: What is the role of rituximab maintenance in patients with low tumor burden follicular lymphoma?

By Peter Martin, MD

The optimal management of patients with newly diagnosed low tumor burden follicular lymphoma is uncertain. In the pre-rituximab era, multiple randomized phase 3 trials demonstrated the acceptability of a period of observation prior to initiation of chemotherapy. This period, which typically lasted for about three years, was considered beneficial because it allowed patients to enjoy a prolonged period of time before experiencing side effects associated with treatment. The development of rituximab led some clinicians to question the value of deferred therapy.

The ECOG 4402 trial (RESORT trial), presented at the American Society of Hematology (ASH) meeting, is a phase 3 trial in which patients with newly diagnosed low tumor burden follicular lymphoma were treated with single-agent rituximab and responders were randomized to either maintenance therapy with one dose of rituximab every three months or rituximab retreatment at the time of lymphoma progression. The goal was to determine which strategy was associated with a longer duration of benefit from rituximab.

At three years of follow-up, 95% of patients receiving maintenance rituximab and 86% of patients randomized to rituximab retreatment remained free of cytotoxic chemotherapy, a significant improvement over historical strategies with observation. Interestingly, despite receiving an average of almost four times as much rituximab (15.8 doses vs. 4.5 doses), patients randomized to maintenance rituximab did not experience a longer time to treatment failure or a better quality of life than those randomized to rituximab retreatment. The investigators concluded that maintenance rituximab should not be considered standard of care in patients with low tumor burden follicular lymphoma treated with single-agent rituximab at the time of diagnosis.

Obinutuzumab (GA101), a New Generation Rituximab

By Peter Martin, MD

Rituximab is a chimeric (human-mouse) monoclonal antibody directed against the protein CD20 on the surface of B-lymphocytes and most B-cell lymphomas. Several clinical trials have demonstrated that rituximab can increase response rates, prolong remissions, and improve survival among patients with various B-cell lymphomas and is an FDA-approved drug. Interestingly, rituximab was developed during an era when our understanding of how monoclonal antibodies might work was relatively naïve. Obinutuzumab (GA101) is a newer generation anti-CD20 antibody that has undergone significant engineering to capitalize on new knowledge. In preclinical testing, GA101 appeared to work better than rituximab. Three clinical trials evaluating GA101 in patients with follicular lymphoma were presented at the American Society of Hematology (ASH) meeting this year.

Dr. Gilles Salles presented the results of a phase I/II study performed in France, in which patients with indolent non-Hodgkin lymphoma (mostly follicular lymphoma). In phase I of the study, patients were treated with escalating doses of GA101, while in phase 2, patients were randomized between two dose levels (high-dose and low-dose). Most patients had received prior rituximab. Overall, GA101 appeared to be well tolerated, with mild infusion reactions being the most common side effect. The results were encouraging, particularly in the high-dose group, but will need to be confirmed with a larger study and longer follow-up.

Dr. John Radford presented the results of the international GAUDI study, which evaluated the safety and efficacy of combining GA101 with CHOP or FC chemotherapy in patients with previously treated follicular lymphoma. Continue reading “Obinutuzumab (GA101), a New Generation Rituximab”

ASH 2011: New Treatment for T-Cell Lymphoma

By Jia Ruan, MD

Update: The below mentioned trials are closed to enrollment. 

The peripheral T-cell lymphomas (PTCL) are a heterogeneous group of lymphoid diseases that constitute less than 15 percent of all non-Hodgkin lymphomas in adults in North America. The most common subtypes are 1) Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS); 2) Anaplastic large cell lymphoma, primary systemic type (ALCL); and 3) Angioimmunoblastic T-cell lymphoma (AITL).  The PTCLs are generally aggressive, and tend to run a more relapsing and less favorable clinical course compared to B-cell NHLs.  Relapsed and refractory diseases are common. Novel and target therapies are in much need.

At the recent Annual Society of Hematology (ASH) meeting, Dr. Friedberg of the University of Rochester reported the result of a phase 2 trial of Alisertib (MLN8237), a potent inhibitor of aurora A kinase, in patients with relapsed aggressive non-Hodgkin’s lymphoma (NHL). Aurora kinases regulate mitosis during cell division. Inhibition of aurora A kinase can lead to mitotic errors and premature cell death. Alisertib is taken orally twice daily for 7 days on 21-day cycles. This phase 2 study enrolled a total of 48 patients, including 8 patients with peripheral T-cell lymphoma. The overall response rate was 32%.  Response in T-cell NHL was the most impressive at 57%: four out of eight patients responded, and the some of the responses were durable. The response rates in DLBCL and MCL were modest around 20%. Treatment-related side effects were generally tolerable and included low blood counts, fever, fatigue and inflammation in mouth. Based on these results, additional clinical trials (phase II sponsored by SWOG / NCI and phase III sponsored by Millennium) with this orally available compound are moving forward in T-cell lymphoma. Both of these studies will be available soon at Weill Cornell Medical College  (click here to read about the SWOG/NCI trial and click here to read about the Millennium trial on clinicaltrials.gov).

Dr. Advani of Stanford University discussed the updated results of an international phase 2 study of Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large cell lymphoma Continue reading “ASH 2011: New Treatment for T-Cell Lymphoma”

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