Bendamustine and Rituximab to Treat Mantle Cell Lymphoma

Atlanta—A phase 2, single-arm, multicenter study found that patients with mantle cell lymphoma who had received up to 3 prior courses of chemotherapy had an overall response rate of 82% to the combination treatment of bendamustine plus rituximab. The authors noted that patients had acceptable tolerance to the therapy.

Results were presented during a poster session at the ASH meeting. The poster was titled Open-Label Bendamustine Combined with Rituximab for Treatment of Relapsed/Refractory Mantle Cell Lymphoma: Efficacy and Safety Findings.

According to the authors, there is no standard of care to treat mantle cell lymphoma, an aggressive subtype of non-Hodgkin’s lymphoma. They said patients who undergo chemotherapy typically have a tumor response, although few are cured and median survival is 3 to 5 years.

In 2 previous small studies, the combination of bendamustine (an alkylating agent) and rituximab (a monoclonal antibody) led to high overall survival and good response rates in patients with mantle cell lymphoma, the authors noted.

This trial included 47 adults (≥18 years of age) with relapsed/refractory, CD20-positive, ß-cell mantle cell lymphoma. They received 90 mg/m² of bendamustine administered intravenously on days 1 and 2 and 375 mg/m² of rituximab administered intravenously on day 1 of a 28-day cycle. Patients received six, 28-day treatment cycles; those without disease progression and without a complete response received up to 8 cycles. At baseline, and at the end of treatment, they underwent magnetic resonance imaging.

Exclusion criteria included patients who received >3 prior chemotherapy regimens, had a prior high-dose chemotherapy regimen with allogeneic stem cell support or radiation immunotherapy, and had New York Heart Association class III or IV heart failure, arrhythmias, unstable angina, or myocardial infarction within 6 months.

Of the 47 patients, 45 received ≥1 dose of bendamustine plus rituximab, although 3 patients discontinued after disease progression, 2 discontinued due to an adverse event, 1 discontinued due to thrombocytopenia and back pain, and 1 discontinued after experiencing grade 5 myocardial infarction, pneumonia, and respiratory failure.

Median age of patients was 71 years, 71% were males, and 82% had stage IV disease. They received a median of 6 cycles of treatment, with a range of 1 to 8 cycles.

The overall response rate using 2008 International Working Group criteria was 82%, with 38% of patients achieving a complete response and 44% achieving a partial response. Patients with relapsed mantle cell lymphoma had a 91% overall response rate compared with 74% for patients with refractory mantle cell lymphoma.

Median progression-free survival was 16.4 months, and 62% of patients had progression-free survival after 1 year. Median duration of response was 14.5 months. At 3 years, the rate of overall survival had not been reached.

Of the 45 patients, 11 had a dose reduction of bendamustine but none needed to have their rituximab dose reduced. In addition, 24 patients had ≥1 dose delay, with 29% of patients experiencing a delay of 3 to 7 days, 33% of patients having a delay of 8 to 14 days, 21% of patients having a delay of 14 to 21 days, and 17% of patients having a delay of 21 to 28 days. The most common reasons for the delay were neutropenia and thrombocytopenia.

Further, 91% of patients had an adverse event, with the most frequent grade 3 or 4 hematologic toxicities being lymphopenia, leucopenia, and neutropenia and the most frequent nonhematologic grade 3 or 4 adverse events being hypokalemia, hypotension, muscular weakness, and pneumonia. Seventeen patients had serious adverse events, and 1 person died during the study after experiencing myocardial infarction, pneumonia, and respiratory failure. The authors said the death was not related to the study treatment.

This study was sponsored and conducted by Teva Pharmaceutical Industries Ltd.