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Bendamustine plus rituximab for previously untreated patients with indolent B-cell non-Hodgkin lymphoma or mantle cell lymphoma: a multicenter Phase II clinical trial in Japan

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Abstract

A Phase II, multicenter clinical trial of bendamustine plus rituximab (BR) regimen was conducted in previously untreated patients with high-tumor-burden indolent B-cell non-Hodgkin lymphoma (B-NHL) and previously untreated elderly patients with mantle cell lymphoma (MCL) in Japan. Bendamustine 90 mg/m2/day on days 1 and 2, as well as rituximab 375 mg/m2 on day 1 were administered intravenously up to six cycles. The primary endpoint was the complete response (CR) rate as assessed by the International Workshop Response Criteria (1999). Sixty-nine patients (59 with indolent B-NHL and 10 with MCL) were treated. The median number of delivered cycles was six (range 1–6). The CR rates were 67.8% [95% confidence interval (CI) 54.4–79.4%] and 70.0% (95% CI 34.8–93.3%) for indolent B-NHL and MCL, respectively. Estimated progression-free survival at 30 months was 72.1% (95% CI 58.5–82.0%) in indolent B-NHL and was 67.5% (95% CI 29.1–88.2%) in MCL. Major grade 3/4 toxicities were hematologic and included lymphopenia (97%), CD4 lymphopenia (91%), neutropenia (86%), and leukopenia (83%). No treatment-related death was found. The BR regimen showed high efficacy as evidenced by the expected CR rate and durable response, as well as an acceptable safety profile for the study populations.

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Acknowledgements

We thank patients, investigators, and staff who were involved in the present study. Research support was provided by SymBio Pharmaceuticals Ltd. We also thank Satoshi Sakima, MD, for his gracious review of the manuscript. This work was supported by SymBio Pharmaceuticals Ltd. and Eisai Co., Ltd.

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Correspondence to Michinori Ogura.

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Dr. Ogura has received research funding from SymBio; and has received honoraria from Takeda, Mundipharma, Meiji Seika Pharma, and Celgene. Dr. Ishizawa has received research funding from Kyowa Hakko Kirin, MSD, Celgene, and Pfizer; and has received honoraria form Kyowa Hakko Kirin, Chugai, and Takeda. Dr. Maruyama has received honoraria from Eisai, Takeda, Chugai, Janssen, Nippon Kayaku, Celgene, Mundipharma, Sanofi, Kyowa Hakko Kirin, Mochida, and Ono. Dr. Ando has received research funding form Kyowa Hakko Kirin. Dr. Izutsu has received honoraria and research funding from Eisai. Dr. Terui has received honoraria form Janssen. Dr. Tsukasaki has received research funding from Eisai, Celgene, Takeda, and Mundipharma; and has received honoraria from Zenyaku Kogyo, HUYA, and Chugai. Dr. Usuki has received honoraria from Nippon Shinyaku, MSD, Kyowa Hakko Kirin, Novartis, Bristol-Meyer-Squibb, and Dainippon Sumitomo. Dr. Kinoshita has received research funding form Eisai, Solasia, and has received honoraria from Eisai, Zenyaku Kogyo, Janssen, Chugai, and Kyowa Hakko Kirin. Dr. Suzumiya has received research funding from Eisai, Kyowa Hakko Kirin, Chugai, Astellas, and Toyama Chemical; and has received honoraria from Eisai, Chugai, and Takeda. Dr. Nagai has received research funding from CIMIC, Janssen, Mundipharma, Takeda, Bristol-Myers Squibb, and Otsuka; and has received honoraria from Chugai. GY has received honoraria form Takeda, Celgene, and Janssen. Dr. Tobinai has received research funding from Eisai, Chugai, Kyowa Hakko Kirin, Ono, Celgene, Janssen, GlaxoSmithKline, Mundipharma, Takeda, Servier, and AbbVie; and has received honoraria from Eisai, Janssen, Mundipharma, Takeda, Zenyaku Kogyo, and HUYA.

All remaining authors have declared no conflicts of interest.

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Ogura, M., Ishizawa, K., Maruyama, D. et al. Bendamustine plus rituximab for previously untreated patients with indolent B-cell non-Hodgkin lymphoma or mantle cell lymphoma: a multicenter Phase II clinical trial in Japan. Int J Hematol 105, 470–477 (2017). https://doi.org/10.1007/s12185-016-2146-4

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