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Reduced frequency treatment with bortezomib plus dexamethasone for elderly patients with relapsed and/or refractory multiple myeloma: a phase 2 study of the Japanese Myeloma Study Group (JMSG-0902)

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Abstract

Bortezomib is one of the most widely used novel drugs for the treatment of multiple myeloma (MM). However, twice-weekly intravenous administration is associated with innegligible adverse events and treatment discontinuation. We therefore evaluated the long-term efficacy and feasibility of reduced frequency treatment with intravenous bortezomib in elderly patients with relapsed and/or refractory MM. A total of 47 bortezomib-naïve patients (median age 75 years) received bortezomib (1.3 mg/m2, intravenously) and dexamethasone (20 mg) on days 1, 8, and 15 of every 4-week cycle. Twenty-six patients completed the planned 8 cycles. Best responses were stringent complete response (sCR) in 5 patients, very good partial response (VGPR) in 3, PR in 15, stable disease (SD) in 18, and disease progression (PD) in 6, respectively. Median progression-free and overall survivals were 9.6 and 35.1 months, respectively. After progression, 11 patients were retreated with bortezomib-based regimens and another 24 patients with immunomodulatory drugs. Multivariate analysis revealed that ISS 3, t(4;14), and <4 therapy cycles were significantly poor prognostic factors and that subsequent therapy with bortezomib-based regimens was a favorable factor for extended OS. The common adverse events were diarrhea, constipation, and peripheral neuropathy with no grade 4 toxicity. In conclusion, reduced frequency treatment with intravenous bortezomib + dexamethasone is an effective option for elderly patients with MM.

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Acknowledgments

We thank the physicians and medical staffs who participated in this study. Study investigators were as follows: Shuji Ozaki, Etsuko Sekimoto, Hironobu Shibata, and Toshio Shigekiyo, Department of Hematology, Tokushima Prefectural Central Hospital, Tokushima; Kazutaka Sunami, Shoji Asakura, Jun Konishi, Shiro Kubonishi, Tomoko Inomata, and Haruto Yamada, Department of Hematology, NHO Okayama Medical Center, Okayama; Morio Sawamura, Morio Matsumoto, Momoko Mawatari, Akio Saitou, and Akinori Yuzuriha, Department of Hematology, NHO Nishigunma Hospital; Shibukawa; Hiroki Yano, Takahiro Imaizumi, and Yu Asao, Department of Hematology, Kainan Hospital, Aichi Prefectural Welfare Federation of Agricultural Cooperatives, Yatomi; Hiroshi Kosugi, Naoyuki Tange, Masaaki Yuge, and Takeshi Kanematsu, Department of Hematology, Ogaki Municipal Hospital, Ogaki; Tomonori Nakazato, Department of Hematology, Yokohama Municipal Citizen’s Hospital, Yokohama; Taro Masunari, Department of Hematology, Chugoku Central Hospital, Fukuyama; Hideki Tsujimura and Kyoya Kumagai, Division of Hematology-Oncology, Chiba Cancer Center, Chiba; Takeshi Harada and Masahiro Abe, Department of Hematology, Tokushima University Hospital, Tokushima; Toshiaki Hayashi and Tadao Ishida, First Department of Internal Medicine, Sapporo Medical University Hospital, Sapporo; Tadahiko Igarashi, Division of Hematology and Oncology, Gunma Prefectural Cancer Center, Ohta; Hideto Tamura, Department of Hematology, Nippon Medical School Hospital, Tokyo; Ichiro Hanamura, Masuya Watarai, and Miyuki Takahashi, Department of Hematology, Aichi Medical University Hospital, Nagakute; Akira Katsumi and Miki Kobayashi, Division of Transfusion Medicine and Cell Therapy, National Center for Geriatrics and Gerontology, Obu; Toshiro Kurokawa, Department of Hematology, Toyama Red Cross Hospital, Toyama; Chihiro Shimazaki and Akira Okuno, Department of Hematology, JCHO Kyoto Kuramaguchi Medical Center, Kyoto, Japan

We also thank Advanced Clinical Research Organization and Ryoji Nakamura for their excellent support. This work was supported in part by a grant from the International Myeloma Foundation (IMF) Japan.

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Authors and Affiliations

  1. Department of Hematology, Tokushima Prefectural Central Hospital, 1-10-3 Kuramoto, Tokushima, 770-8539, Japan

    Shuji Ozaki

  2. Division of Informative Clinical Sciences, Kumamoto University, Kumamoto, Japan

    Hiroyuki Hata

  3. Department of Medicine and Bioregulatory Sciences, University of Tokushima, Tokushima, Japan

    Masahiro Abe

  4. Department of Laboratory Sciences, Graduate School of Health Sciences, Gunma University, Maebashi, Japan

    Takayuki Saitoh & Hirokazu Murakami

  5. Department of Hematology, Aichi Medical University, Nagakute, Japan

    Ichiro Hanamura

  6. Department of Hematology, Kainan Hospital, Aichi Prefectural Welfare Federation of Agricultural Cooperatives, Yatomi, Japan

    Hiroki Yano

  7. Department of Hematology, NHO Okayama Medical Center, Okayama, Japan

    Kazutaka Sunami

  8. Department of Hematology, Ogaki Municipal Hospital, Ogaki, Japan

    Hiroshi Kosugi

  9. Department of Hematology, NHO Nishigunma Hospital, Shibukawa, Japan

    Morio Sawamura

  10. Department of Hematology, Yokohama Municipal Citizen’s Hospital, Yokohama, Japan

    Tomonori Nakazato

  11. Department of Hematology, Chugoku Central Hospital, Fukuyama, Japan

    Taro Masunari

  12. Tama-Hokubu Medical Center, Higashimurayama, Japan

    Mayumi Mori

  13. Department of Hematology and Oncology, Kimitsu Chuo Hospital, Kisarazu, Japan

    Toshiyuki Takagi

  14. Department of Hematology, Tokai Central Hospital, Kakamigahara, Japan

    Kazuyuki Shimizu

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  1. Shuji Ozaki
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  2. Hiroyuki Hata
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  3. Masahiro Abe
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  7. Kazutaka Sunami
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  8. Hiroshi Kosugi
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  9. Morio Sawamura
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  11. Taro Masunari
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  12. Mayumi Mori
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  14. Hirokazu Murakami
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  15. Kazuyuki Shimizu
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Corresponding author

Correspondence to Shuji Ozaki.

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Conflict of interest

KS received research funding from Ono Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Novartis Pharmaceutical Co. Ltd., and Celgene Co. Ltd.

Additional information

This trial was registered at the UMIN Clinical Trial Registry (UMIN 000003345)

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Ozaki, S., Hata, H., Abe, M. et al. Reduced frequency treatment with bortezomib plus dexamethasone for elderly patients with relapsed and/or refractory multiple myeloma: a phase 2 study of the Japanese Myeloma Study Group (JMSG-0902). Ann Hematol 95, 921–929 (2016). https://doi.org/10.1007/s00277-016-2661-7

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  • DOI: https://doi.org/10.1007/s00277-016-2661-7

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