Bendamustine-120 plus rituximab therapy for relapsed or refractory follicular lymphoma: a multicenter phase II study
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The optimal dose, schedule, and other aspects of bendamustine plus rituximab treatment remain unclear for patients with relapsed or refractory follicular lymphoma (FL). Herein, we analyzed the efficacy of bendamustine combined with rituximab (RB-120) treatment for Japanese patients with relapsed or refractory FL. This phase II clinical trial included patients with relapsed or refractory FL who received 375 mg/m2 rituximab on day 1 and 120 mg/m2 bendamustine on days 2 and 3 every 28 days for up to 6 cycles. The primary endpoint was the overall response rate (ORR), and the secondary endpoints included the complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and safety. Thirty-seven patients were enrolled in the trial (median age 62 years, range 42–75 years). All patients were previously treated with rituximab-containing chemotherapy, and 83.8% were previously treated with the R-CHOP regimen. A median of 5 cycles (range 1–6) and 48.6% of patients completed 6 cycles. The ORR was 91.9% (95% confidence interval [CI] 78.1–98.3%), with a CR rate of 86.5% (95% CI 71.2–95.5%). The 3-year PFS and OS were 70.9% (95% CI 52.3–83.3%) and 88.9% (95% CI 73.1–95.7%), respectively, with the median 39.5 months follow-up duration. The most-frequently observed grade 3/4 adverse events were hematologic: lymphopenia (95%) and neutropenia (70%). No treatment-related deaths were observed. RB-120 showed a good efficacy with equivalent toxicities, compared with the bendamustine 120 mg/m2 monotherapy. However, the problem of high drop-out incidences cannot be ignored.
KeywordsFollicular lymphoma Relapsed Refractory Bendamustine Rituximab
The authors would like to thank the patients and their families, the investigators, and staff who participated in this multicenter trial for their excellent cooperation. We also thank Atsuko Yoshizawa, Etsuo Miyaoka, and the staff of the Department of Mathematics, Faculty of Science, Tokyo University of Science, for their technical assistance with data management.
This study was funded by the Translational Research Network Program, Project of Translational and Clinical Research Core Centers (University of Tokyo), Japan Agency for Medical Research and Development, AMED.
Compliance with ethical standards
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments.
Conflict of interest
Dr. Sakai has received research funding from Chugai, Kyowa Hakko Kirin, Ono, Yakult, Taiho, and Eisai and honoraria from Takeda, Bayer, Bristol-Meyer-Squibb, Sumitomo Dainippon, Celgene, Mundipharma, Eisai, and Kyowa Hakko Kirin. Dr. Ohmachi has received honoraria from Chugai, Kyowa Hakko Kirin, Eisai, Pfizer, Takeda, Celgene, and Meiji Seika. Dr. Sano has received research funding from Chugai and Kyowa Hakko Kirin and honoraria from Celgene, Janssen, Bristol-Meyer-Squibb, Eisai, Pfizer, Chugai, and Alexion. Dr. Takasaki has received honoraria from Kyowa Hakko Kirin, Eisai, and Janssen. Dr. Miyazaki has received research funding from Astellas. Dr. Yamamot has received honoraria from Celgene, Janssen, Kyowa Hakko Kirin, Bristol-Meyer-Squibb, MSD, Meiji Seika, Novartis, Shaire Japan, Alexion, and Chugai. Dr. Tomita has received research funding from Terumo Foundation for Life Sciences and Arts. Dr. Ando has received research funding from Kyowa Hakko Kirin, Eisai, Bristol-Meyer-Squibb, Novartis, and Takeda. All remaining authors have declared no conflicts of interest.
Informed consent was obtained from all individual participants included in the study.
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