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Clinical impacts of frailty, poor performance status, and advanced age in carfilzomib-containing treatment for relapsed/refractory multiple myeloma: post hoc investigation of the KOTOSG multicenter pilot prospective observational study

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Abstract

We conducted a post hoc analysis of our previous pilot observational study on the efficacy and safety of carfilzomib (CFZ)-containing therapy in 50 patients with relapsed/refractory multiple myeloma in routine practice to clarify the relationships between three major criteria for vulnerability (frailty, poor performance status [PS], and advanced age [≥ 75 years]) and their clinical impact on efficacy and adverse events (AEs). Sixteen patients fulfilled at least one and five patients fulfilled all three criteria. The overall response rate was not significantly affected by frailty, poor PS, and/or advanced age; however, frailty and advanced age were significantly associated with shorter progression-free survival (PFS). In contrast, no significant difference in PFS was observed between patients with PS0–1 or PS2–4. The three criteria for vulnerability were associated with more frequent hematologic AEs: frailty, poor PS, and/or advanced age significantly increased the risk of grade 3–4 anemia and lymphopenia. However, these criteria were not associated with increased risk of other non-hematologic AEs except infection. Collectively, these results demonstrate the need to carefully manage severe hematologic AEs in vulnerable patients and perform disease-specific assessment of frailty to predict prognosis.

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Acknowledgements

We thank all the researchers in the Kyoto Clinical Hematology Study Group for their scientific support. This work was funded by Ono Pharmaceutical Co., Ltd.

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Author notes

  1. Yuka Kawaji-Kanayama and Ayako Muramatsu contributed equal to this study.

Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan

    Yuka Kawaji-Kanayama, Ayako Muramatsu, Reiko Isa, Takahiro Fujino, Yayoi Matsumura-Kimoto, Taku Tsukamoto, Yoshiaki Chinen, Shinsuke Mizutani, Yuji Shimura, Tsutomu Kobayashi, Masafumi Taniwaki & Junya Kuroda

  2. Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan

    Nana Sasaki & Nobuhiko Uoshima

  3. Department of Hematology, Aiseikai Yamashina Hospital, Kyoto, Japan

    Kazuho Shimura, Hiroto Kaneko & Masafumi Taniwaki

  4. Department of Hematology, Matsushita Memorial Hospital, Moriguchi, Japan

    Miki Kiyota & Eri Kawata

  5. Department of Hematology, Japan Community Health Care Organization, Kyoto Kuramaguchi Medical Center, Kyoto, Japan

    Shinichi Fuchida & Chihiro Shimazaki

  6. Department of Internal Medicine, Otsu Municipal Hospital, Otsu, Japan

    Mitsushige Nakao

  7. Department of Hematology, Fukuchiyama City Hospital, Fukuchiyama, Japan

    Koichi Hirakawa

  8. Department of Hematology, Omihachiman Community Medical Center, Omihachiman, Japan

    Ryoichi Takahashi

  9. Department of Hematology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan

    Hitoji Uchiyama

  10. Department of Blood Transfusion, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Yuji Shimura

  11. Center for Molecular Diagnostics and Therapeutics, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Masafumi Taniwaki

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  1. Yuka Kawaji-Kanayama
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  2. Ayako Muramatsu
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Consortia

Kyoto Clinical Hematology Study Group (KOTOSG) Investigators

Contributions

YK, AM, TK, and JK analyzed and interpreted the data. JK and TK were involved in the study conception and design. YK, AM, NS, KS, MK, SF, RI, TF, YM, TT, YC, SM, MN, HK, EK, KH, RT, CS, HU, NO, and YS were involved in data acquisition. TK and YK performed statistical analysis. YK drafted the manuscript. JK revised the manuscript. MT and JK supervised the research. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Junya Kuroda.

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Conflict of interest

This study is supported by Ono Pharmaceutical. J.K. has received research funding from Bristol-Myers Squibb, Sysmex, Ono Pharmaceutical, Sanofi, Takeda, Fujimoto Pharmaceutical, and Abbvie; has received honoraria from Bristol-Myers Squibb, Janssen Pharmaceutical K.K, Ono Pharmaceutical, Takeda, Sanofi, Fujimoto Pharmaceutical, and Abbvie; and is a consultant for Janssen Pharmaceutical K.K, and Bristol-Myers Squibb. T.K. has received honoraria from Ono Pharmaceutical. M.T. has received honoraria from Bristol-Myers Squibb. N.U. has received honoraria from Bristol-Myers Squibb and Takeda. S.F. has received honoraria from Takeda, Ono Pharmaceutical, Bristol-Myers Squibb, Sanofi, and Janssen Pharmaceutical. All other authors have no conflict of interest.

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Kawaji-Kanayama, Y., Muramatsu, A., Sasaki, N. et al. Clinical impacts of frailty, poor performance status, and advanced age in carfilzomib-containing treatment for relapsed/refractory multiple myeloma: post hoc investigation of the KOTOSG multicenter pilot prospective observational study. Int J Hematol 115, 350–362 (2022). https://doi.org/10.1007/s12185-021-03262-z

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