Rituximab, bendamustine, and lenalidomide in patients with aggressive B cell lymphoma not eligible for high-dose chemotherapy or anthracycline-based therapy: phase I results of the SAKK 38/08 trial
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This phase I trial was designed to develop a new effective and well-tolerated regimen for patients with aggressive B cell lymphoma not eligible for front-line anthracycline-based chemotherapy or aggressive second-line treatment strategies. The combination of rituximab (375 mg/m2 on day 1), bendamustine (70 mg/m2 on days 1 and 2), and lenalidomide was tested with a dose escalation of lenalidomide at three dose levels (10, 15, or 20 mg/day) using a 3 + 3 design. Courses were repeated every 4 weeks. The recommended dose was defined as one level below the dose level identifying ≥2/6 patients with a dose-limiting toxicity (DLT) during the first cycle. Thirteen patients were eligible for analysis. Median age was 77 years. WHO performance status was 0 or 1 in 12 patients. The Charlson Comorbidity Index showed relevant comorbidities in all patients. Two DLTs occurred at the second dose level (15 mg/day) within the first cycle: one patient had prolonged grade 3 neutropenia, and one patient experienced grade 4 cardiac adverse event (myocardial infarction). Additional grade 3 and 4 toxicities were as follows: neutropenia (31 %), thrombocytopenia (23 %), cardiac toxicity (31 %), fatigue (15 %), and rash (15 %). The dose of lenalidomide of 10 mg/day was recommended for a subsequent phase II in combination with rituximab 375 mg/m2 on day 1 and bendamustine 70 mg/m2 on days 1 and 2.
KeywordsAggressive B cell lymphoma Relapse Elderly Rituximab Bendamustine Lenalidomide
This trial was sponsored by the Swiss Group for Clinical Cancer Research (SAKK). SAKK was responsible for the study design, study conduct, analysis, and manuscript writing. Roche Pharma (Schweiz) AG, Mundipharma Medical Company (Schweiz), and Celgene GmbH supported the study in part financially, supplied the study drug, and offered comments in the process of manuscript writing. This trial was also supported by the Swiss State Secretariat for Education and Research (SER).
Conflict of interest
EZ has participation in the Roche and Celgene advisory boards. All other authors declare no conflict of interest.
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