Bendamustine Is Safe and Effective in Patients with Rituximab-Refractory, Indolent B-Cell Non-Hodgkin Lymphoma.

Background: Bendamustine (Treanda®) is a purine analog/alkylator hybrid with single-agent activity in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), multiple myeloma, and breast cancer. The objective of this phase 3 multicenter study was to evaluate the efficacy and safety of single-agent bendamustine HCl in patients with relapsed, rituximab-refractory NHL.

Methods: Eligible patients had previously treated, rituximab-refractory, indolent-histology NHL. Rituximab-refractory was defined as no response or progression within 6 months of

1. first dose of rituximab induction,

2. completion of rituximab maintenance therapy or progression before the next scheduled rituximab dose, or

3. completion of a combination of rituximab and chemotherapy.

Patients received bendamustine 120 mg/m² intravenously over 60 minutes on days 1 and 2 every 21 days for 6 cycles (2 additional cycles at investigator discretion; max 8). Tumor response was determined by modified International Working Group Response Criteria for NHL. The primary endpoint was overall response rate (ORR) with secondary endpoints of response duration (RD) and progression-free survival (PFS).

Results: Results for the first 38 of 100 enrolled patients are presented. The median age was 60 years, 63% were male, and 63% had stage III/IV disease. Histologies included follicular (53%), CLL/small lymphocytic lymphoma (26%), and marginal zone (21%) lymphoma. Patients had received a median of 3 prior courses of treatment (range 1–10) and 2 prior rituximab-containing courses (range 1–6). Prior alkylator or purine analog-based treatment was administered to 79% and 37% of patients, respectively. Eighteen (47%) patients were considered to be chemoresistant. Four (11%) patients received prior radioimmunotherapy. The ORR in the primary analysis population was 84%, including 29% complete responses (CR), 3% CR unconfirmed, and 53% partial responses. The median RD was 9.3 months and the median PFS was 9.7 months. The primary hematologic toxicity was reversible myelosuppression; grade 3/4 hematologic side effects included leukopenia (60%), neutropenia (60%), thrombocytopenia (24%), lymphocytopenia (95%), and anemia (5%). Febrile neutropenia was not observed. Common nonhematologic adverse events (grades 1/2, 3, 4) were nausea (68%, 5%, 0%), vomiting (42%, 0%, 0%), and fatigue (42%, 13%, 3%).

Conclusions: In this multicenter study, single-agent bendamustine was well tolerated and produced a high rate (84%) of durable responses. It is the first chemotherapeutic agent to demonstrate significant clinical activity in rituximab-refractory indolent lymphoma. These results compare favorably with prior reports of radioimmunotherapy in this patient population. An updated analysis of all 100 patients will be available for the annual meeting.