SUMMARY: Mantle cell lymphomas constitute approximately 5% of all Non Hodgkins lymphomas and have a high relapse rate following dose-intensive therapies. Bortezomib (VELCADE®) is approved for the treatment of relapsed mantle cell myeloma (MCL) and has a response rate of 30%. This open label, phase II trial, evaluated the safety and efficacy of Lenalidomide (REVLIMID®) in 134 patients with MCL who have had prior therapy with Rituximab (RITUXAN®), Cyclophosphamide, Anthracycline and had relapsed or progressed in less than 12 months or were refractory to VELCADE®. Patients had a median of 4 prior treatments. Treatment consisted of single agent REVLIMID® 25 mg/day given on days 1 thru 21 of a 28-day cycle, given until disease progression or unacceptable toxicity. The primary endpoints were overall response rate (ORR) and duration of response. The secondary endpoints included complete response (CR), Progression Free Survival (PFS), time to progression, overall survival (OS) and safety. In this heavily pretreated patient population the ORR was 28% and the median duration of response of 16.6 months. The CR was 8%, PFS was 4.0 months, and OS was 19.0 months. The most common grade 3/4 adverse events were cytopenias. The authors concluded that REVLIMID® resulted in rapid and durable responses in patients with relapsed/refractory MCL. Goy A, Sinha R, Williams ME, et al. 54th ASH Annual Meeting and Exposition 2012, Abstract 905
Tag: Non-Hodgkin Lymphoma
RITUXAN® (Rituximab)
The FDA on October 19, 2012 approved a 90-minute infusion for RITUXAN® (Rituximab) starting at Cycle 2 for patients with non-Hodgkin’s lymphoma (NHL) who did not experience a grade 3 or 4 infusion-related adverse reaction during Cycle 1. Patients with clinically significant cardiovascular disease and high circulating lymphocyte counts (>5000/mcL) are not recommended to receive the faster infusion. RITUXAN® is a product of Genentech, Inc.
Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent and mantle cell lymphomas (MCL) Updated results from the StiL NHL1 study
SUMMARY: This is an updated analysis of a study initially presented at ASH 2009 meeting. TREANDA® (Bendamustine) is an alkylating agent presently indicated for the treatment of patients with Chronic Lymphocytic Leukemia (CLL) as well as Indolent B-cell non-Hodgkin’s lymphoma (NHL) that has progressed during 
or within six months of treatment with RITUXAN® (Rituximab) or a RITUXAN® containing regimen. In this randomized phase III trial, TREANDA® plus RITUXAN® (B-R)was compared to R-CHOP as first line treatment for patients with indolent or MCL. The primary endpoint was Progression Free Survival (PFS). With a median follow up of 45 months, patients on B-R had a PFS of 69.5 months vs 31.2 months for R-CHOP (HR =0.58; P<0.001). This benefit was seen in all age groups and all histological subtypes except marginal zone lymphoma. B-R was better tolerated than R-CHOP. There was no difference in the overall survival between the two groups. It should be noted however that close to 50% of the patients on R-CHOP whose disease progressed, were permitted to cross over to B-R and this could have impacted the overall survival results. Rummel MJ, Niederle N, Maschmeyer G, et al. J Clin Oncol 30, 2012 (suppl; abstr 3)
Brentuximab vedotin (SGN-35) for Hodgkin’s Lymphoma and Anaplastic large Cell Lymphoma
Brentuximab vedotin (SGN-35) is an antibody-drug conjugate (ADC) that targets CD30, which is a protein expressed on cancer cells in patients with Hodgkin’s lymphoma (HL) as well as Anaplastic Large Cell Lymphoma (ALCL), an aggressive type of T-cell non-Hodgkin’s lymphoma. This ADC consists of an anti-CD30 monoclonal antibody linked to monomethyl auristatin E (MMAE), an antimicrotubule agent. Upon binding to the CD30 molecule on the cancer cells, MMAE is released into the cancer cell resulting in cell death.
Taking advantage of this dual action, targeted mechanism of action of brentuximab vedotin , two phase II studies were conducted, one in patients with relapsed or refractory HL and the other in patients with relapsed or refractory systemic ALCL. In the HL pivotal trial, 102 relapsed or refractory Hodgkin lymphoma patients who had failed prior autologous stem cell transplant (ASCT) had an overall objective response rate of 75% and 34% of the patients went into complete remission (CR). In the second phase II trial, of the 58 patients with relapsed or refractory systemic ALCL, 86% achieved an objective response and 57% went into CR.
Based on these data, the Oncologic Drugs Advisory Committee (ODAC) voted 10-0 to recommend that the FDA grant accelerated approval of brentuximab vedotin. The results from the above two studies will change the treatment paradigm in this difficult to treat patient population.
Rituximab maintenance for 2 years in patients with untreated high tumor burden follicular lymphoma after response to immunochemotherapy
SUMMARY: The FDA in January, 2011 approved rituximab (RITUXAN®) as a maintenance treatment for patients with advanced follicular lymphoma. Follicular lymphomas are a subset of Non Hodgkins Lymphomas and are very responsive to chemotherapy or chemotherapy given along with RITUXAN®. They are however incurable, despite treatment with RITUXAN® plus chemotherapy. This condition can therefore be considered as a chronic disease. For this reason, prolonging remission duration is important, as the length of remission tends to be shorter with each recurrence. The FDA approval was based on the PRIMA trial, which is a phase III study, in which 1217 treatment naive patients with stage III and stage IV disease requiring therapy were initially treated with RITUXAN® and chemotherapy (induction chemotherapy). Patients responding to initial therapy (n = 1018) were randomized to observation alone or maintenance RITUXAN® for 2 years. The first preplanned interim analysis at a median follow up of 25 months demonstrated a progression-free survival (PFS) of 82% in the RITUXAN® maintenance therapy group versus 66% for those in the observation group, which meant that the recurrence rate was 18% with RITUXAN® maintenance versus 34% for those who were observed. This benefit with RITUXAN® maintenance therapy was seen regardless of age, disease severity, and type of induction chemotherapy received. These findings are relevant, as these patients essentially have a chronic disease and are willing to pursue interventions that could potentially delay recurrence of their lymphoma and thus improve their quality of lives. J Clin Oncol 28:15s, 2010 (suppl; abstr 8004))
Maintenance Rituximab
The FDA on Jan 31, 2011 approved Rituximab as a maintenance treatment for patients with advanced follicular lymphoma, who responded to initial treatment with Rituximab plus chemotherapy. Follicular lymphomas are a subset of Non Hodgkins Lymphomas and are very responsive to chemotherapy or chemotherapy with Rituximab. They are usually incurable however, despite treatment with Rituximab plus chemotherapy. So think of this condition as a chronic disease. For this reason, prolonging remission duration is important, as the length of remission tends to be shorter with each recurrence.
In the PRIMA trial, which was a phase III study, maintenance Rituximab for 2 years given to those who responded to induction treatment with chemotherapy and Rituximab, delayed the risk of recurrence and improved progression free survival. These findings are relevant for patients who essentially have a chronic disease and are willing to pursue interventions that would delay recurrence of their lymphoma and therefore improve their quality of lives.