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

• Published in: Annals of hematology Vol. 92; no. 8; pp. 1033 - 1040
• Main Authors: Hitz, F., Fischer, N., Pabst, Th, Caspar, C., Berthod, G., Eckhardt, K., Berardi Vilei, S., Zucca, E., Mey, U.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2013; Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived - administration & dosage; Antibodies, Monoclonal, Murine-Derived - adverse effects; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bendamustine Hydrochloride; Comorbidity; Dose-Response Relationship, Drug; Drug Eruptions - etiology; Fatigue - chemically induced; Female; Heart Diseases - chemically induced; Hematologic Diseases - chemically induced; Hematology; Humans; Lymphoma, B-Cell - drug therapy; Lymphoma, Non-Hodgkin - drug therapy; Male; Medicine; Medicine & Public Health; Nitrogen Mustard Compounds - administration & dosage; Nitrogen Mustard Compounds - adverse effects; Oncology; Original Article; Rituximab; Salvage Therapy; Thalidomide - administration & dosage; Thalidomide - adverse effects; Thalidomide - analogs & derivatives; Treatment Outcome; Rituximab; Aggressive B cell lymphoma; Relapse; Bendamustine; Lenalidomide; Elderly
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-013-1751-z

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/m 2 on day 1), bendamustine (70 mg/m 2 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/m 2 on day 1 and bendamustine 70 mg/m 2 on days 1 and 2.