Phase II Results of Bendamustine in Combination with Rituximab in Relapsed Indolent and Mantle-Cell Non-Hodgkin’s Lymphoma.

Objective: The objective of this study was to evaluate the efficacy and safety of bendamustine HCl (TREANDA^®) in combination with rituximab in patients with relapsed non-Hodgkin’s lymphoma (NHL).

Background: Bendamustine is a novel hybrid, alkylating agent with single-agent activity in multiple hematologic and solid tumors. It induces cell death via both apoptosis and the apoptosis-independent pathway of mitotic catastrophe. The combination of bendamustine and rituximab has been shown to exhibit a synergistic antitumor effect on NHL cells.

Methods: This Phase II, multicenter study enrolled adult patients with relapsed, indolent B-cell or mantle-cell NHL who were not refractory to rituximab (defined as progression ≤6 months of last rituximab dose). Patients received rituximab 375 mg/m² intravenously (IV) on day 1 and bendamustine 90 mg/m² IV on days 2 and 3 of a 28-day cycle for 4 to 6 cycles. An additional dose of rituximab 375 mg/m² IV was given 1 week before the first cycle of bendamustine and 4 weeks after the last cycle.

Results: The intent-to-treat (ITT) population included 66 patients (59% men) with a median age of 60 years (range, 40–84). Indolent histologic phenotype was seen in 54 patients with the following histologic subtypes: follicular center cell (61%), small lymphocytic (15%), lymphoplasmacytic (3%), and marginal zone (3%); 18% had mantle-cell lymphoma (MCL). A total of 85% of patients had stage III/IV disease. These patients relapsed from a median of 1 prior chemotherapy (range: 0–5), with 56% having had prior treatment with rituximab. Patients with no prior chemotherapy relapsed following biologic therapy. In the ITT population, the overall objective response rate (ORR) was 94% (complete response [CR]/complete response unconfirmed [CRu], 41%; partial response [PR], 53%); 6% had stable disease. The ORR for the 12 MCL patients was 92% (CR/CRu, 42%; PR 50%). For all patients, the median duration of response and progression-free survival has not been reached after a median follow-up of 8.3 months (range, 0.14–31 months). Grade 3/4 neutropenia was seen in 41% of patients (7%, febrile neutropenia). Common nonhematologic toxicities (grade 1/2, grade 3, grade 4) were nausea (68%, 0%, 0%) and fatigue (53%, 5%, 0%); one patient had grade 3 sepsis. No alopecia was observed.

Conclusions: Bendamustine administered in combination with rituximab produced a high objective response rate and was generally well tolerated in patients with relapsed indolent and mantle-cell NHL who were not refractory to rituximab. These results suggest that the combination of bendamustine and rituximab may be comparable in activity to R-CHOP, and further studies of this combination are warranted.