PB2008 AN OPEN-LABEL STUDY OF BENDAMUSTINE HYDROCHLORIDE IN CHINESE PATIENTS WITH INDOLENT NON-HODGKIN LYMPHOMA (NHL) REFRACTORY TO RITUXIMAB TREATMENT
Authors: Y. Shi, X. Hong, H. Huang, W. Xu, X. Han, J. Yang, E. Hellriegel, L. James
Journal: HemaSphere (2019)

Background: Bendamustine hydrochloride (Treanda®) is approved globally for multiple forms of B-cell malignancy. Aims: Examine the efficacy and safety of bendamustine in Chinese patients with indolent B-cell non-Hodgkin lymphoma (iNHL) relapsed following a rituximab-containing regimen. Methods: INHL patients relapsed after rituximab treatment received bendamustine 120 mg/m2 IV infusion on day 1 and 2 of each 21-day cycle up to 8 cycles. Two years of data were collected. The primary endpoints was overall response rate (ORR); secondary endpoints were duration of response (DOR), progression-free survival (PFS), pharmacokinetics (PK), and safety data. Results: A total of 102 patients were enrolled during the initial study period; 76 (75%) patients continued to the 2-year follow-up period. Of the 102 patients, 24 (24%) completed the study (defined as completing the follow-up period alive without progression) whereas 78 (77%) did not complete the study for the following reasons: 49 (48%) had disease progression, 9 (9%) withdrew, 3 (3%) were lost to follow-up, 5 (5%) died, and 13 for other reasons. The ORR was 73% (95% CI: 62.82-80.92) per independent review committee (IRC) including 21% complete response (CR) and 52% partial response (PR). The ORR per investigator assessment was 78% (31% CR and 47% 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 16.2 months (95% CI: 9.3-NA) per IRC and 13.4 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 treatment; at the end of follow-up, the 75th percentile was 20.7 months. The median PFS was 18.6 months and was similar across baseline characteristics. PK analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnic populations. Total systemic exposure (AUC0∞) to M3 was approximately 1/10 of that to bendamustine and approximately 10-fold higher than M4. The overall safety profile was consistent with known adverse events (AEs). The most common AEs were white blood cell count decreased (54%), neutrophil count decreased (47%), neutropenia (46%), leukopenia (45%), nausea (44%), and platelet count decreased (40%). Severe AEs of respiratory failure, pneumonia, lung infection, and herpes virus infection were reported. A total of 4 patients had AEs reported during follow-up. Five patients died during the study, 3 of which were attributed to bendamustine (respiratory failure, lung infection and hemoptysis). Thirty patients had serious AEs and 25 patients had AEs that resulted in discontinued treatment. Summary/Conclusion: The results show a clinical benefit and provide support for the use of bendamustine as a single-agent treatment for patients with rituximab-refractory, relapsed, iNHL. Given the relatively high incidence of respiratory failure and serious infections in this study, which may not be explained by bone marrow suppression alone, physicians should pay attention to the risk of lung injury and immunosuppression. Further research on the mechanisms of these events is warranted.