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Pembrolizumab plus lenalidomide and dexamethasone in treatment-naive multiple myeloma (KEYNOTE-185): subgroup analysis in Japanese patients

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Abstract

The global, randomized, open-label KEYNOTE-185 study closed early after an interim analysis showed an unfavorable benefit-risk profile with pembrolizumab plus lenalidomide and low-dose dexamethasone (Rd) versus Rd alone in treatment-naive, transplant-ineligible multiple myeloma. This subgroup analysis reported outcomes in the Japanese population. Patients were randomly assigned (1:1) to pembrolizumab plus Rd or Rd alone, stratified by age and International Staging System. The primary end point was progression-free survival (PFS). Fifty-two Japanese patients were randomly assigned to pembrolizumab plus Rd (n = 27) or Rd (n = 25). The median follow-up was 7.2 months (range, 0.4–13.8). The median PFS was not reached (NR); 6-month PFS was 91.2% versus 86.2% with pembrolizumab plus Rd versus Rd [hazard ratio (HR), 0.31; 95% CI, 0.06–1.63]. The median overall survival (OS) was NR; 6-month OS was 96.2% versus 95.7% with pembrolizumab plus Rd versus Rd (HR, 0.33; 95% CI, 0.03–3.72). With pembrolizumab plus Rd versus Rd, grade 3–5 adverse events occurred in 70.4% versus 69.6% of patients; serious adverse events occurred in 40.7% versus 52.5%. Although in the Japanese subgroup of KEYNOTE-185 adding pembrolizumab to Rd did not show an unfavorable risk-benefit, the analysis is limited by short follow-up and small sample size, affecting generalizability of the results.

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Acknowledgements

The authors thank the patients and their families and caregivers for contributing to this study. The authors also acknowledge the investigators, site personnel, and personnel of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, who supported this study. Medical writing and/or editorial assistance was provided by Julia Burke, PhD, and Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

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Authors and Affiliations

  1. National Hospital Organization Disaster Medical Center, 3256 Midori, Tachikawa, Tokyo, Japan

    Naoki Takezako

  2. Ogaki Municipal Hospital, Ogaki, Japan

    Hiroshi Kosugi

  3. National Hospital Organization, Shibukawa Medical Center, Shibukawa, Japan

    Morio Matsumoto

  4. Nagoya City University Hospital, Nagoya, Japan

    Shinsuke Iida

  5. Kobe City Medical Center, Kobe, Japan

    Takayuki Ishikawa

  6. Kanazawa University Hospital, Kanazawa, Japan

    Yukio Kondo

  7. Tokai University School of Medicine, Isehara, Japan

    Kiyoshi Ando

  8. Tokushima University Hospital, Tokushima, Japan

    Hirokazu Miki

  9. Kindai University Hospital, Osaka-Sayama, Japan

    Itaru Matsumura

  10. National Hospital Organization Okayama Medical Center, Okayama, Japan

    Kazutaka Sunami

  11. Hokkaido University Hospital, Sapporo, Japan

    Takanori Teshima

  12. National Hospital Organization Kyushu Medical Center, Fukuoka, Japan

    Hiromi Iwasaki

  13. Tohoku University Hospital, Sendai, Japan

    Yasushi Onishi

  14. Saitama Medical Center, Saitama Medical University, Kawagoe-shi, Japan

    Masahiro Kizaki

  15. National Cancer Center Hospital, Tokyo, Japan

    Koji Izutsu, Dai Maruyama & Kensei Tobinai

  16. Merck & Co., Inc., Kentilworth, NJ, USA

    Razi Ghori, Mohammed Farooqui, Jason Liao & Patricia Marinello

  17. MSD K.K, Tokyo, Japan

    Kenji Matsuda, Yasuhiro Koh & Takashi Shimamoto

  18. Japanese Red Cross Medical Center, Tokyo, Japan

    Kenshi Suzuki

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  1. Naoki Takezako
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Contributions

N.T.: acquisition of the data, interpretation of the results, critically reviewing or revising the manuscript for important intellectual content. H.K.: analysis and acquisition of the data, interpretation of the results, critically reviewing or revising the manuscript for important intellectual content. M.M.: acquisition of the data, interpretation of the results, critically reviewing or revising the manuscript for important intellectual content. S.I.: acquisition of the data, interpretation of the results, reviewing or revising the manuscript for important intellectual content. T.I.: acquisition of the data, interpretation of the results, critically reviewing or revising the manuscript for important intellectual content. Y.K.: acquisition of the data, reviewing or revising the manuscript for important intellectual content. K.A.: Interpretation of the results, reviewing or revising the manuscript for important intellectual content. H.M.: interpretation of the results, drafting of the manuscript, reviewing or revising the manuscript for important intellectual content. I.M.: acquisition of the data, critically reviewing or revising the manuscript for important intellectual content. K.S.: acquisition of the data, reviewing or revising the manuscript for important intellectual content. T.T.: acquisition of the data, interpretation of the results, reviewing or revising the manuscript for important intellectual content. H.I.: acquisition of the data, critically reviewing or revising the manuscript for important intellectual content. Y.O.: interpretation of the results, critically reviewing or revising the manuscript for important intellectual content. M.K.: interpretation of the results, critically reviewing or revising the manuscript for important intellectual content. K.I.: acquisition of the data, critically reviewing or revising the manuscript for important intellectual content. D.M.: acquisition of the data, interpretation of the results, critically reviewing or revising the manuscript for important intellectual content. K.T.: acquisition of the data, interpretation of the results, drafting of the manuscript, critically reviewing or revising the manuscript for important intellectual content. R.G.: conception, design or planning of the study, acquisition and analysis of the data, interpretation of the results, critically reviewing or revising the manuscript for important intellectual content. M.F.: acquisition and analysis of the data, interpretation of the results, critically reviewing or revising the manuscript for important intellectual content. J.L.: Conception, design or planning of the study, analysis of the data, interpretation of the results, critically reviewing or revising the manuscript for important intellectual content. P.M.: conception, design or planning of the study, analysis of the data, interpretation of the results, critically reviewing or revising the manuscript for important intellectual content. K.M.: conception, design or planning of the study, acquisition and analysis of the data, interpretation of the results, drafting of the manuscript, critically reviewing or revising the manuscript for important intellectual content. Y.K.: conception, design or planning of the study, analysis of the data, interpretation of the results, drafting of the manuscript, critically reviewing or revising the manuscript for important intellectual content. T.S.: conception, design or planning of the study, acquisition and analysis of the data, interpretation of the results, critically reviewing or revising the manuscript for important intellectual content. K.S.: conception, design or planning of the study, drafting of the manuscript. All authors approved the final version of the manuscript.

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Correspondence to Naoki Takezako.

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Takezako, N., Kosugi, H., Matsumoto, M. et al. Pembrolizumab plus lenalidomide and dexamethasone in treatment-naive multiple myeloma (KEYNOTE-185): subgroup analysis in Japanese patients. Int J Hematol 112, 640–649 (2020). https://doi.org/10.1007/s12185-020-02953-3

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