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Elotuzumab plus lenalidomide and dexamethasone for newly diagnosed multiple myeloma: a randomized, open-label, phase 2 study in Japan

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Abstract

Novel therapies are needed for patients with newly diagnosed multiple myeloma (NDMM). Elotuzumab plus lenalidomide and dexamethasone (ELd) is approved for the treatment of relapsed/refractory multiple myeloma (RRMM). This phase 2 study in Japan evaluated ELd vs lenalidomide and dexamethasone (Ld) in patients with NDMM who were ineligible for stem cell transplantation. Elotuzumab infusion was accelerated to 5 mL/min by dose 3, cycle 1, allowing most subsequent infusions to be completed within 1 h. The primary endpoint was overall response rate (ORR) in the ELd arm. Secondary endpoints were the difference in ORR between treatments, and progression-free survival (PFS). Patients were randomized to ELd (n = 40) or Ld (n = 42); median number of treatment cycles was 13 (ELd) and 12 (Ld). In the ELd arm, ORR was 88% [70% confidence interval (CI) 80–93]. The estimated difference in ORR between treatments was 13% (95% CI  − 4, 30) in favor of ELd. Progression-free survival data were immature. Safety was consistent with previous findings of ELd in Japanese patients with RRMM. No infusion reactions occurred at the maximum rate of 5 mL/min, which was used in 89% of elotuzumab infusions. ELd may be an effective, well-tolerated frontline treatment for patients with NDMM ineligible for stem cell transplantation.

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Acknowledgements

The study was funded by Bristol-Myers Squibb K.K. Under the direction of the authors, professional medical writing assistance in the form of writing the first draft, drafting figures and tables, and collating author comments was provided by Laura Yee of Caudex, funded by Bristol-Myers Squibb K.K.

Funding

The study sponsor, Bristol-Myers Squibb K.K., provided the study drug and collaborated with the investigators to design the study and to collect and analyze the data. Editorial assistance from professional medical writers was funded by the sponsor.

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Authors and Affiliations

  1. Department of Hematology, Aomori Prefectural Central Hospital, 2-1-1 Higashi-Tsukurimichi, Aomori, 030-8553, Japan

    Kohmei Kubo

  2. Department of Hematology, Ibaraki Prefectural Central Hospital, Kasama, Japan

    Mitsuo Hori

  3. Department of Hematology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan

    Kensuke Ohta

  4. Hematology Ohta Clinic, Shinsaibashi, Osaka, Japan

    Kensuke Ohta

  5. Department of Hematology, Gunma University Hospital, Maebashi, Japan

    Hiroshi Handa

  6. Department of Lymphoma/Hematologic Malignancy Center, Mita Hospital, International University of Health and Welfare, Tokyo, Japan

    Kiyohiko Hatake

  7. Department of Hematology, National Hospital Organization Shibukawa Medical Center, Shibukawa, Japan

    Morio Matsumoto

  8. Division of Hematology, Internal Medicine, National Center for Global Health and Medicine Hospital, Tokyo, Japan

    Shotaro Hagiwara

  9. Department of Hematology, Tokyo Women’s Medical University, Tokyo, Japan

    Shotaro Hagiwara

  10. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan

    Kazuteru Ohashi

  11. Department of Hematology, Chiba University Hospital, Chiba, Japan

    Chiaki Nakaseko

  12. Department of Hematology, School of Medicine, International University of Health and Welfare, Narita, Japan

    Chiaki Nakaseko

  13. Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan

    Kenshi Suzuki

  14. Department of Clinical Oncology, Iwate Medical University Hospital, Morioka, Japan

    Shigeki Ito

  15. Bristol-Myers Squibb K.K., Tokyo, Japan

    Gen Kinoshita & Masafumi Miyoshi

  16. Bristol-Myers Squibb, Princeton, NJ, USA

    Suresh G. Shelat

  17. Department of Hematology, National Hospital Organization Disaster Medical Center, Tokyo, Japan

    Naoki Takezako

Authors
  1. Kohmei Kubo
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  2. Mitsuo Hori
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  3. Kensuke Ohta
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  4. Hiroshi Handa
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Contributions

KK, MH, KO, HH, KH, MM, SH, KO, CN, KS, SI, and NT participated in data acquisition. GK performed data analysis. GK, SGS, and MM contributed to the conception and design of the study. All authors participated in interpreting the data, critically reviewed the manuscript, and approved the final version for submission.

Corresponding author

Correspondence to Kohmei Kubo.

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Conflict of interest

MH reports post-marketing surveillance study fees from Celgene, Fujifilm RI Pharma, and Shire Japan. K Ohta reports honoraria from Bristol-Myers Squibb K.K., Celgene K.K., Janssen Pharmaceutical K.K., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd, and Takeda Pharmaceutical Co. Ltd. HH reports research grants from Celgene, Takeda Pharmaceutical, Astellas Pharma, Daiichi Sankyo, Sanofi, MSD, Kyowa Hakko Kirin, Chugai Pharmaceutical, Pfizer, Otsuka Pharmaceutical, and Ono Pharmaceutical, and honoraria from Celgene, Takeda Pharmaceutical, Daiichi Sankyo and Ono Pharmaceutical. KH reports honoraria from Bristol-Myers Squibb K.K., Ono Pharmaceutical Co. Ltd, Takeda Pharmaceutical Co. Ltd., Taiho Pharmaceutical, Johnson & Johnson, Celgene, AbbVie, Eisai, MSD, Kyowa Hakko Kirin, Novartis and Chugai Pharmaceutical, and consultancy from Otsuka Pharmaceutical and Meiji Seika Pharma. M Matsumoto reports honoraria from Janssen Pharmaceutical, Celgene, Takeda Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb K.K., Daiichi Sankyo, and Kyowa Hakko Kirin. SH reports a grant for investigator sponsored research from Bristol-Myers Squibb K.K. CN reports honoraria from Bristol-Myers Squibb K.K., Celgene K.K., Janssen Pharmaceutical K.K., Novartis Pharma K.K., and Takeda Pharmaceutical Co. Ltd, and research funding from Bristol-Myers Squibb K.K., Ono Pharmaceutical Co. Ltd, and Takeda Pharmaceutical Co. Ltd. KS reports personal fees from Celgene, Janssen Pharmaceutical, Takeda, Novartis, Bristol-Myers Squibb K.K., and Sanofi. SI reports honoraria from Bristol-Myers Squibb K.K., Celgene K.K., Janssen Pharmaceutical K.K., Ono Pharmaceutical Co. Ltd, and Takeda Pharmaceutical Co. Ltd. GK and M Miyoshi report employment by Bristol-Myers Squibb K.K. SGS reports employment by and equity ownership in Bristol-Myers Squibb. K.K., K Ohashi, and NT declare no competing financial interests.

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Kubo, K., Hori, M., Ohta, K. et al. Elotuzumab plus lenalidomide and dexamethasone for newly diagnosed multiple myeloma: a randomized, open-label, phase 2 study in Japan. Int J Hematol 111, 65–74 (2020). https://doi.org/10.1007/s12185-019-02757-0

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