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Analysis of Japanese patients from the AUGMENT phase III study of lenalidomide + rituximab (R2) vs. rituximab + placebo in relapsed/refractory indolent non-Hodgkin lymphoma

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A Letter to the Editor to this article was published on 04 September 2020

Abstract

Patients with indolent non-Hodgkin lymphoma (iNHL) typically respond to first-line immunochemotherapy, but relapse is common. Treatment options for relapsed iNHL include chemotherapy ± rituximab and rituximab monotherapy. Lenalidomide plus rituximab (R2) is an immunomodulatory regimen that enhances rituximab-mediated cytotoxicity and improves clinical activity in iNHL. AUGMENT was a double-blind phase III randomized trial of R2 vs. rituximab + placebo (R-placebo) in patients with relapsed/refractory follicular lymphoma or marginal zone lymphoma who were not refractory to rituximab. The primary endpoint was progression-free survival (PFS). Data reported here focus on Japanese patients from AUGMENT and reflect 36 patients (n = 18, each group). PFS was superior in the R2 group, HR = 0.32 (95% CI 0.11–0.96). Median PFS was not reached (95% CI 19.7–NE) in the R2 group vs. 16.5 months (95% CI 11.3–30.6) in the R-placebo group. Grade 3/4 adverse events were more frequent in patients treated with R2 (67%) than with R-placebo (22%), primarily attributable to increased neutropenia (50% vs 17%). R2 resulted in significantly longer median PFS than R-placebo in Japanese patients with R/R iNHL, and the efficacy and the safety profile of R2 were similar to those reported in the global population.

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Acknowledgements

All authors performed and/or designed the research study, analyzed the data, contributed to the development and revision of the manuscript, and approved the final version for submission. The authors thank the patients, their family members, and collaborators from participating institutions and Celgene Corporation. Thank you to following investigators for their participation in data collection at each site: Drs. Kenichi Ishizawa, Yoko Okitsu, Satoshi Ichikawa, Kunihiro Tsukasaki, Takayuki Yoshino, Kiyohiko Hatake, Dai Maruyama, and Masafumi Taniwaki. Medical writing support was provided by Benjamin Levine, PhD of Bio Connections LLC, and funded by Celgene Corporation; the authors were fully responsible for content and editorial decisions for this manuscript.

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Authors and Affiliations

  1. Department of Hematology, National Cancer Center Hospital, 5-1-1 Tsukji, Chou-ku, Tokyo, 104-0045, Japan

    Koji Izutsu & Kensei Tobinai

  2. Department of Hematology, National Cancer Center Hospital East, Chiba, Japan

    Yosuke Minami

  3. Department of Hematology and Rheumatology, Tohoku University Hospital, Sendai, Japan

    Noriko Fukuhara

  4. Department of Hematology Oncology, The Cancer Institute Hospital of JFCR, Tokyo, Japan

    Yasuhito Terui

  5. Department of Hematology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan

    Tatsuro Jo

  6. Department of Hematology, Toranomon Hospital, Tokyo, Japan

    Go Yamamoto

  7. Kobe City Medical Center General Hospital, Hematology, Kobe, Japan

    Takayuki Ishikawa

  8. Division of Hematology and Oncology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Tsutomu Kobayashi

  9. Department of Hematology, Chugoku Central Hospital, Fukuyama, Japan

    Toru Kiguchi

  10. Department of Hematology and Oncology Research, Nagoya Medical Center, Clinical Research Center, Nagoya, Japan

    Hirokazu Nagai

  11. Celgene K.K., Tokyo, Japan

    Tomoko Ohtsu & Shuichi Midorikawa

  12. Celgene Corporation, Summit, NJ, USA

    Stacey Kalambakas

  13. Celgene Corporation, Boudry, Switzerland

    Pierre Fustier

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  1. Koji Izutsu
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Correspondence to Koji Izutsu.

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Conflict of interest

KI reports grants from Celgene during the conduct of the study; grants and personal fees from Celgene, Eisai, MSD, Takeda, Janssen, Mundipharma, Chugai, Astra Zeneca, Abbvie, Bayer, and Zenyaku outside the submitted work; personal fees from Bristol Myers Squib, Dainihon Sumitomo, Nihon Mediphysics, and Kyowa Hakko Kirin outside the submitted work; and grants from Ono, Gilead, Solasia, Symbio, Astellas Amgen, and Daiichi Sankyo outside the submitted work. YM reports research funding from Ono Pharmaceutical and lecture fees from BMS, Novartis, and Pfizer outside the submitted work. NF reports grants from Celgene K.K. during the conduct of the study; grants and personal fees from Eisai and Takeda outside the submitted work; grants from Abbvie, Bayer, Gilead and Solasia Pharma outside the submitted work; and personal fees from Celgene, Chugai, Janssen, Kyowa Hakko Kirin, Mochida, Mundi, Nippon Shinyaku, Ono and Zenyaku outside the submitted work. GY reports personal fees from Celgene, Kyowa Hakko Kirin, Takeda, Bristol-Myers Squibb, Mundipharma, and Janssen outside the submitted work; and grants and personal fees from Chugai Pharma and Eisai outside the submitted work. HN reports grants from Celgene Corporation during the conduct of the study; grants and personal fees from Janssen Pharmaceutical K. K, Celgene Corporation, Mundipharma K.K., Bayer Yakuhin, Takeda Pharmaceutical, Kyowa Hakko Kirin, Esai, Bristol-Myers Squibb, Ono Pharmaceutical, Gilead Sciences, Zenyaku Kogyo, AstraZeneca, SymBio Pharmaceuticals, Otsuka Pharmaceutical, and Roche; grants from Abbvie G.K., Solasia Pharma K.K., HUYA Bioscience International, IQVIA Japan K.K.; and personal fees from Sanofi K.K. outside the submitted work. TO reports employment and stockholder with Celgene K.K. during the conduct of the study. SK reports employment and stockholder with Celgene during the conduct of the study. PF reports employment, stockholder, and received personal fees from Celgene during the conduct of the study. SM reports employment with Celgene K.K. and stockholder of Celgene. KT reports grants and personal fees from Celgene during the conduct of the study; personal fees from Zenyaku, HUYA Bioscience International, Yakult, Daiichi Sanky, Bristol-Myers Squibb, Meiji Seika Kaisha, Solasia Pharma, and Verastem outside the submitted work; grants from Janssen and Abbvie outside the submitted work; and grants and personal fees from Eisai, Takeda, Mundipharma, Kyowa Hakko Kirin, Chugai Pharma, and Ono Pharmaceutical outside the submitted work. YT, TJ, TI, TKo, and TKi report no conflict of interest.

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Supplementary Fig. 1

Duration of response, as assessed by IRC (TIF 131 kb)

Supplementary Fig. 2

Event-free survival, as assessed by IRC (TIF 132 kb)

Supplementary Fig. 3

Time to next anti-lymphoma treatment (TIF 130 kb)

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Izutsu, K., Minami, Y., Fukuhara, N. et al. Analysis of Japanese patients from the AUGMENT phase III study of lenalidomide + rituximab (R2) vs. rituximab + placebo in relapsed/refractory indolent non-Hodgkin lymphoma. Int J Hematol 111, 409–416 (2020). https://doi.org/10.1007/s12185-019-02802-y

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