Open-Label Study of Bendamustine Hydrochloride in Chinese Patients with Indolent Non-Hodgkin Lymphoma (NHL) Refractory to Rituximab Treatment

Introduction: The addition of rituximab to chemotherapy has been associated with substantial responses in patients with indolent NHL, but patients usually relapse. Bendamustine hydrochloride (bendamustine; Treanda®) is an alkylating agent approved globally for multiple indications including chronic lymphocytic leukemia, indolent B-cell NHL, mantel cell lymphoma, and multiple myeloma. This open-label, single-arm, multicenter study in China aims to determine the overall response rate (ORR) to bendamustine treatment in patients with indolent B-cell NHL refractory to a rituximab-containing regimen.

Methods: Patients with documented relapse from indolent B-cell NHL after rituximab treatment and 1-3 previous chemotherapy regimens were included. Patients received bendamustine intravenous 120 mg/m² infusion (over 60 minutes) on day 1 and 2 of each 21-day cycle for at least 6 cycles and were allowed to continue treatment for up to 8 cycles. Primary endpoint was response rate based on the modified International Workshop Response Criteria; secondary endpoints were duration of response (DOR), progression-free survival (PFS), and safety.

Results: A total of 102 patients from 20 centers were enrolled. All enrolled patients were analyzed for safety and efficacy. The ORR was 73% (95% CI: 62.82-80.92) per independent review committee (IRC) including 19% complete response (CR) and 54% partial response (PR). The ORR per investigator assessment was 78% (30% CR and 48% PR). Among 31 patients with disease refractory to last alkylator therapy, the ORR was 68% (95% CI: 48.63-83.32). The median DOR was 16.5 months (95% CI: 10.9-NA) per IRC and 12.5 months per investigator. Durable responses were observed across all baseline patient and disease characteristics. Median DOR was not reached in patients refractory to last alkylator or chemotherapy treatment. The median PFS was 18.6 months and was similar across baseline characteristics. Disease characteristics did not significantly impact PFS.

The overall safety profile was consistent with known adverse events (AEs). The most common AEs (≥40%) were white blood cell count decreased (54%), neutrophil count decreased (47%), neutropenia (46%), leukopenia (45%), nausea (44%), and platelet count decreased (40%). Most patients completed planned treatment; the mean relative dose intensity was 82%. Neutropenia was the most common reason for dose reductions. Four patients died during the study, three of which were attributed to bendamustine. At least one serious AE was experienced by 29 patients, and AEs that resulted in discontinued treatment occurred in 25 patients.

Conclusions: Single-agent bendamustine is effective in the treatment of Chinese patients with rituximab-refractory, relapsed indolent B-cell NHL including those with previous alkylator exposure, with a safety profile consistent with known AEs.

Sponsor: Teva Branded Pharmaceutical Products R&D