Bendamustine Produces Durable Responses With an Acceptable Safety Profile in Patients With Rituximab-Refractory Indolent Non-Hodgkin Lymphoma

Background: Although initially responsive to therapy, indolent non-Hodgkin lymphomas (NHLs) are generally incurable. Therefore, active and tolerable treatments for patients with relapsed or refractory disease are needed. Bendamustine, a mechlorethamine alkylator with novel mechanisms of action, is approved in the United States for rituximab-refractory indolent B-cell NHL. Patients and Methods: Data from 2 North American multicenter studies with similar design, enrollment, and response criteria were pooled to evaluate safety and durability of response. Bendamustine was administered at 120 mg/m(2) days 1 and 2 every 21 days for 6-8 cycles. Endpoints included overall response rate (OAR), duration of response (DOR), progression-free survival (PFS), and safety. Results: The studies enrolled 161 patients with a median of 2 previous chemotherapy regimens. Histologies included follicular (68%), small lymphocytic (20%), marginal zone (11%), and lymphoplasmacytic (1%) lymphoma. Sixty patients (34.1%) were refractory to their last chemotherapy, 53 (30.1%) were alkylating agent refractory. Overall response rate was 76% with 23% complete remissions (CRs) and unconfirmed CR (CRu). The median follow-up was 25.3 months (range, 24-27.8 months) and DOR was 10 months (range, 8.3-14 months). At 1 and 2 years, 45% and 23% of responders continued to respond. Among 127 patients previously treated with alkylators, OAR was 88% (28% CR/CRu) in responsive and 59% (12% CR/CRu) in refractory patients. Fifty opportunistic infections were reported in 48 patients. Second malignances occurred in 9 patients (5.6%; 5 myelodysplastic syndromes, 2 acute myelogenous leukemia, 1 chronic myelomonocytic leukemia, and 1 squamous cell carcinoma). Conclusion: Bendamustine induces durable responses with acceptable long-term safety in rituximab-refractory indolent NHL.