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Daratumumab, lenalidomide, and dexamethasone in Japanese patients with transplant-ineligible newly diagnosed multiple myeloma: a phase 1b study

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Abstract

Lenalidomide and dexamethasone (Rd) treatment is common for patients with newly diagnosed multiple myeloma (NDMM) ineligible for autologous stem-cell transplantation. Daratumumab plus Rd (D-Rd) is effective and well tolerated for treating relapsed or refractory multiple myeloma. In this ongoing phase 1b trial, transplant-ineligible Japanese patients with NDMM received daratumumab (16 mg/kg intravenously every week for 8 weeks, every 2 weeks for 16 weeks, then every 4 weeks until disease progression) plus Rd (R 25 mg on Days 1‒21 of 28-day cycle; d 40 mg weekly). The primary objective was to evaluate D-Rd tolerability and safety in Japanese patients with NDMM. Secondary objectives included daratumumab pharmacokinetics and response rate. During the dose-limiting toxicity (DLT) evaluation period, two DLTs occurred in seven (28.6%) patients, indicating D-Rd tolerability. At an 11.0-month median follow-up (interim analysis), grade 3/4 treatment-emergent adverse events occurred in six (85.7%) patients, including lymphopenia (71.4%), leukopenia (57.1%), and neutropenia (42.9%). Three (42.9%) patients experienced infusion-related reactions (IRRs). All IRRs were grade 2, occurred during the first daratumumab infusion, and resolved within 24 h. Pharmacokinetic findings were comparable to those in previous studies. A 100% overall response rate was achieved. These findings suggest D-Rd is tolerable in Japanese patients with transplant-ineligible NDMM. ClinicalTrials.gov identifier NCT02918331.

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Data availability

The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at https://yoda.yale.edu.

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Acknowledgements

This study was sponsored by Janssen Pharmaceutical K.K. The authors would like to acknowledge Hidehisa Noguchi for contributions to statistical analyses, and Akiko Suzuki, Hiromi Koga, and Ryo Tamamura for critical review of the manuscript. Medical writing support was provided by J. Matthew Kuczmarski, PhD, and Jill E. Kolesar, PhD, of MedErgy, and was funded by Janssen Global Services, LLC.

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Authors and Affiliations

  1. Department of Hematology, Faculty of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan

    Hiroyuki Takamatsu

  2. Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Shinsuke Iida

  3. Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Suita, Japan

    Hirohiko Shibayama 

  4. Janssen Pharmaceutical K.K., Research & Development Division, Tokyo, Japan

    Kazuhiro Shibayama & Hiroshi Yamazaki

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

    Kenshi Suzuki

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  1. Hiroyuki Takamatsu
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  2. Shinsuke Iida
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  3. Hirohiko Shibayama 
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  4. Kazuhiro Shibayama
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All authors made substantive contributions to experimental design, data acquisition and/or analysis, and critical revision of the manuscript. All authors read and approved the final manuscript for submission.

Corresponding author

Correspondence to Hiroyuki Takamatsu.

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Conflict of interest

Hiroyuki Takamatsu received honoraria from Janssen Pharmaceutical K.K., Celgene, Takeda, Ono Pharmaceutical, Bristol-Myers Squibb, Daiichi Sankyo Company, Fujimoto Pharmaceutical, and Sanofi; received research funds from Celgene, Ono Pharmaceutical, Bristol-Myers Squibb, and CSL Behring; and consulted for Janssen, Celgene, AbbVie, and Sanofi. Shinsuke Iida received honoraria and research funds from Janssen, Celgene, Ono, Takeda, Novartis, Daiichi Sankyo, and Bristol-Myers Squibb; and received research funds from Chugai, Sanofi, MSD, AbbVie, Gilead, Kyowa Hakko Kirin, Astellas, and Teijin Pharma. Hirohiko Shibayama received honoraria and research funds from Takeda, Ono, Eisai, Sumitomo Dainippon Pharma, Mundipharma, and Nippon Shinyaku; received honoraria from Janssen, Celgene, Novartis, Chugai, Kyowa Kirin, Otsuka, AstraZeneca, AbbVie, Daiichi Sankyo, Fujimoto, Sanofi, Bristol-Myers Squibb, and Pfizer; and received research funds from Astellas, Teijin, MSD, Shionogi, and Taiho. Kazuhiro Shibayama and Hiroshi Yamazaki are employees of Janssen Pharmaceutical K.K. Kenshi Suzuki received honoraria from Celgene, Takeda, Amgen, Novartis, Genesis Pharmaceuticals, and Janssen; and received honoraria and research funds from Bristol-Myers Squibb.

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Takamatsu, H., Iida, S., Shibayama , H. et al. Daratumumab, lenalidomide, and dexamethasone in Japanese patients with transplant-ineligible newly diagnosed multiple myeloma: a phase 1b study. Int J Hematol 111, 692–701 (2020). https://doi.org/10.1007/s12185-020-02825-w

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  • DOI: https://doi.org/10.1007/s12185-020-02825-w

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