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Final results of a phase I study of carfilzomib, lenalidomide, and dexamethasone for heavily pretreated multiple myeloma

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Abstract

We report the final results from a multicenter, open-label phase I study of carfilzomib plus lenalidomide and dexamethasone in Japanese patients with heavily pretreated relapsed and/or refractory multiple myeloma (RRMM). Twenty-six RRMM patients were enrolled and received a median of 4.0 prior regimens; 12/26 patients (46.2%) completed the planned 18 administration cycles (mean number of cycles: 14.5 ± 4.9). The safety profile was consistent with that of previous carfilzomib studies. All patients experienced adverse events (AEs), but no new safety concerns were observed. The most common grade ≥ 3 AEs (incidence: ≥ 10%) were lymphocyte count decreased (46.2%), platelet count decreased (42.3%), and neutrophil count decreased (34.6%). The overall response rate was 88.5% (23/26; 90% confidence interval: 72.8–96.8). Complete response (CR) or better was achieved by 30.8% of patients compared with 3.8% in the interim analysis. The median time to CR or better response was 9.4 months. Median progression-free survival and duration of response were 19.5 months and 20.3 months, respectively. Median overall survival was not reached. Long-term administration of carfilzomib produced deep response and long-term disease control. The combination of carfilzomib plus lenalidomide and dexamethasone was well tolerated and showed promising clinical efficacy for heavily pretreated RRMM patients.

Clinical trial registration

This clinical trial was registered in the database clinicaltrials.jp (clinical trial registration number: Japic CTI 142677).

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Acknowledgements

We thank all study participants and their families. We thank all study sites and investigators. We would also like to thank the medical consultant, Dr. Hirokazu Murakami (Gunma University Graduate School of Health Science, Maebashi), and Dr. Chihiro Shimazaki (Japan Community Health Care Organization Kyoto-Kuramaguchi Medical Center, Kyoto), Dr. Masahiro Kizaki (Saitama Medical Center, Saitama Medical University, Saitama), Dr. Takao Katoh (International University of Health and Welfare, Mita Hospital, Tokyo), Dr. Masahiro Endo (Shizuoka Cancer Center, Nagaizumi), and Dr. Terufumi Kato (Kanagawa Cancer Center, Yokohama) for their review of the clinical data as members of the Efficacy and Safety Evaluation Committee. We also acknowledge the statistical support of Naokazu Gion and Toshiaki Ozaki (Ono Pharmaceutical, Osaka) and the critical review of the manuscript by Amgen (Thousand Oaks). We thank Susan Cottrell, PhD, and Keyra Martinez Dunn, MD, of Edanz Medical Writing for providing medical writing support, which was funded by Ono Pharmaceutical through EMC K.K. in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).

Funding

IS, KS, MR, TC, NT, KS, T Ishida, T Izumi, SO, and SI received grants from Ono Pharmaceutical during the course of this study. MR also received grants and personal fees from Bristol-Myers Squibb, Celgene, Janssen Pharmaceutical, Kyowa Hakko Kirin, Ono Pharmaceutical, and Takeda Pharmaceutical, outside the submitted work, and personal fees from Novartis and Sanofi, outside the submitted work. TC also received personal fees from Ono Pharmaceutical during the course of the study and personal fees from Janssen Pharmaceutical, Ono Pharmaceutical, and Takeda Pharmaceutical, outside the submitted work. NT also received personal fees from Ono Pharmaceutical during the course of this study. KS also received personal fees from Ono Pharmaceutical during the course of this study; grants from AbbVie, Alexion Pharma, Daiichi Sankyo, GlaxoSmithKline, Janssen Pharmaceutical, MSD, Novartis, and Sanofi, outside the submitted work; and grants and personal fees from Bristol-Myers Squibb, Celgene, and Takeda Pharmaceutical, outside the submitted work. T Ishida also received personal fees from Celgene, Janssen Pharmaceutical, Ono Pharmaceutical, and Takeda Pharmaceutical, outside the submitted work. SI also received personal fees from Ono Pharmaceutical during the course of this study; grants and personal fees from Bristol-Myers Squibb, Celgene, Janssen Pharmaceutical, Novartis, and Takeda Pharmaceutical, outside the submitted work; and grants from AbbVie, Chugai Pharmaceutical, Daiichi Sankyo, Gilead Pharmaceutical, Kyowa Hakko Kirin, MSD, and Sanofi, outside the submitted work. YS is an employee of Ono Pharmaceutical. The study was designed under the responsibility of Ono Pharmaceutical, in conjunction with the steering committee; the study was funded by Ono Pharmaceutical; carfilzomib was provided by Ono Pharmaceutical; Ono Pharmaceutical collected and analyzed the data and contributed to the interpretation of the study. All authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Toyohashi Municipal Hospital, 50 Aza Hachiken-nishi, Aotake-cho, Toyohashi, Aichi, 441-8570, Japan

    Isamu Sugiura

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

    Kenshi Suzuki & Tadao Ishida

  3. Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Science, Nagoya, Japan

    Masaki Ri & Shinsuke Iida

  4. Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan

    Takaaki Chou

  5. Department of Hematology, National Hospital Organization Disaster Medical Center, Tachikawa, Japan

    Naoki Takezako

  6. Department of Hematology, National Hospital Organization Okayama Medical Center, Okayama, Japan

    Kazutaka Sunami

  7. Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan

    Tadao Ishida

  8. Department of Hematology, Tochigi Cancer Center, Utsunomiya, Japan

    Tohru Izumi

  9. Department of Hematology, Tokushima Prefectural Central Hospital, Tokushima, Japan

    Shuji Ozaki

  10. Department of Oncology Clinical Development Planning, Ono Pharmaceutical, Osaka, Japan

    Yoshihisa Shumiya

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  1. Isamu Sugiura
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  2. Kenshi Suzuki
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  3. Masaki Ri
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  4. Takaaki Chou
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  8. Tohru Izumi
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  9. Shuji Ozaki
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  10. Yoshihisa Shumiya
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  11. Shinsuke Iida
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Correspondence to Isamu Sugiura.

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Sugiura, I., Suzuki, K., Ri, M. et al. Final results of a phase I study of carfilzomib, lenalidomide, and dexamethasone for heavily pretreated multiple myeloma. Int J Hematol 111, 57–64 (2020). https://doi.org/10.1007/s12185-019-02754-3

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  • DOI: https://doi.org/10.1007/s12185-019-02754-3

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