Tag: rituximab

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”

Update from ASH 2011: Rituximab improves survival in patients with mantle cell lymphoma

By Peter Martin, MD

Until recently, the role of rituximab in treatment of mantle cell lymphoma (MCL) was unclear. Prior randomized trials demonstrated improved response rates to chemotherapy when combined with rituximab, but unlike other lymphomas, it had failed to demonstrate an improvement in survival. Two abstracts presented at the recent American Society of Hematology (ASH) meeting provided encouraging evidence regarding this most-important outcome.

Dr. Simon Rule presented the results of the recent UK National Cancer Research Institute trial comparing fludarabine/cyclophosphamide (FC) to FC plus rituximab (FCR) in patients of all ages with newly diagnosed MCL. The trial enrolled 370 patients with mostly intermediate and high-risk MCL and followed them for an average of 39 months. The addition of rituximab to FC improved response rate, complete response rate, time to progression, and overall survival. Combined with recent evidence from data registry studies and the data that has accumulated from prior trials, it is clear that standard of care first-line treatment of MCL should include rituximab.

Updated results from a European Mantle Cell Lymphoma Network trial (also presented at the meeting in Lugano last summer and discussed by Dr. Rebecca Elstrom in this blog) confirmed that rituximab maintenance administered to patients over 60 years of age after R-CHOP chemotherapy provided a significant survival benefit. Although longer follow-up and confirmatory trials are needed, rituximab maintenance may be considered standard of care for older patients not receiving more aggressive induction/consolidation regimens. The upcoming Intergroup trial for patients over 60 years of age will feature randomization between rituximab maintenance and maintenance with lenalidomide plus rituximab.