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Phase I/II study of bortezomib, lenalidomide, and dexamethasone treatment for relapsed and refractory multiple myeloma

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Abstract

Use of novel agents, including proteasome inhibitors and immunomodulatory drugs, has markedly improved outcomes in multiple myeloma (MM) patients. However, most MM patients eventually relapse and require salvage treatments. We report herein the result of a phase I/II study, performed from 2014 to 2017 to assess the feasibility and efficacy of a maximum tolerated dose (MTD) of lenalidomide (Len) combined with a fixed dose of once weekly subcutaneous (sc) 1.3 mg/m2 of bortezomib plus 20 mg of dexamethasone (scVRd regimen) in relapsed/refractory MM patients in the Japanese population. In the phase I part, dose-limiting toxicities were observed in three of six patients treated with 20 mg of Len; the MTD was accordingly defined as 15 mg in our cohort. In the phase II part, the recommended dose of the scVRD regimen showed a 71.4% best overall response rate, with a median overall survival of 14.8 months and a median progression-free survival of 8 months. Severe adverse events (≥ grade 3) were observed in ~ 15% of the patients, indicating the tolerability and efficacy of the regimen. Less prior treatment was associated with higher probability of durable response. This scVRd regimen may thus be a better fit for MM patients in early-stage relapse.

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Acknowledgements

We thank the medical and nursing staff who cared for the patients at the Fukuoka Blood and Marrow Transplantation Group and provided patients information. We are grateful to professor Koji Yonemoto (Ryukyu University) for the data analysis.

Funding

This study was funded by a Grant-in-Aid for Scientific Research (B) (to T.M., No. 16H05340), a Grant-in-Aid for Scientific Research (C) (to Y.M., No. 17K09906), and a grant from the Regional Medicine Research Foundation (Tochigi, Japan).

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Authors and Affiliations

  1. Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Yasuo Mori, Goichi Yoshimoto, Koichi Akashi & Toshihiro Miyamoto

  2. Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

    Ilseung Choi

  3. Department of Hematology/Oncology, Japan Community Health Care Organization (JCHO) Kyushu Hospital, Fukuoka, Japan

    Tsuyoshi Muta & Ryosuke Ogawa

  4. Department of Transfusion Medicine, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan

    Tsuyoshi Muta

  5. Department of Hematology and Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan

    Satoshi Yamasaki & Hiromi Iwasaki

  6. Department of Hematology, Fukuoka Red Cross Hospital, Fukuoka, Japan

    Kazuki Tanimoto

  7. Department of Hematology, Harasanshin Hospital, Fukuoka, Japan

    Tomohiko Kamimura

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  1. Yasuo Mori
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  2. Ilseung Choi
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  3. Goichi Yoshimoto
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  11. Toshihiro Miyamoto
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Fukuoka Blood and Marrow Transplantation Group

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Correspondence to Toshihiro Miyamoto.

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Conflict of interest

Tomohiko Kamimura, Koichi Akashi, and Toshihiro Miyamoto received honoraria from Janssen and Celgene. The other authors have no conflict of interests to declare.

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Mori, Y., Choi, I., Yoshimoto, G. et al. Phase I/II study of bortezomib, lenalidomide, and dexamethasone treatment for relapsed and refractory multiple myeloma. Int J Hematol 111, 673–680 (2020). https://doi.org/10.1007/s12185-020-02833-w

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  • DOI: https://doi.org/10.1007/s12185-020-02833-w

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