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Evaluation of the Revised International Staging System (R-ISS) in Japanese patients with multiple myeloma


In spite of recent development in the treatment armamentarium for multiple myeloma, overall survival (OS) still depends on risk status and sensitivity to treatment of each patient. We have evaluated the clinical relevance of the Revised International Staging System (R-ISS) by comparing it with the original ISS in 718 Japanese patients. The distribution of patients according to response was similar between the ISS and R-ISS stages. Treatment response was greatly influenced by initial treatment modalities and deeper response was observed more frequently in transplanted patients. The R-ISS discriminated the difference in OS between the stages more distinctly than the ISS (p = 9.0 × 10−15 and p = 4.0 × 10−10, respectively). Differences in OS were clarified by both R-ISS and ISS in non-transplanted patients (p = 2.4 × 10−12 and p = 1.4 × 10−8, respectively), but the ISS failed to distinguish the difference between the stages in transplanted patients (p = 0.13). In contrast, the R-ISS could at least discriminate the excellent prognosis of stage I patients whereas the distinction between stage II and III was not that clear (p = 0.033). The R-ISS stage II encompassed a large number of patients, and the prognosis was heterogeneous depending on the fulfillment of prognostic factors such as LDH and adverse cytogenetics. These results suggest that treatment factors and prognostic factors greatly affect the therapeutic response and outcome, and the R-ISS is superior to ISS in prognostication of both transplant-eligible and -ineligible patients in our current clinical practice.

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The following Japanese Society of Myeloma (JSM) institutions and investigators participated in this study: Tadao Ishida, Department of Gastroenterology, Rheumatology, and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo; Takahiro Kobayashi, Takaya Yamashita, Naoto Takahashi, Department of Hematology, Nephrology and Rheumatology, Akita University Hospital, Akita; Hiroshi Handa, Takayuki Saitoh, Hirokazu Murakami, Department of Hematology, Gunma University Hospital, Maebashi; Atsushi Isoda, Morio Matsumoto, Morio Sawamura, Department of Hematology, National Hospital Organization Nishigunma National Hospital, Shibukawa; Eishi Nogiwa, Department of Internal Medicine, Usui Hospital, Yasunaka: Chiaki Nakaseko, Department of Hematology, Chiba University Hospital, Chiba; Fumihiko Nakamura, Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo; Go Yamamoto, Department of Hematology, Toranomon Hospital, Tokyo; Kenshi Suzuki, Department of Hematology, Japanese Red Cross Medical Center, Tokyo; Shotaro Hagiwara, Division of Hematology, Department of Internal Medicine, National Medical Center for Global Health and Medicine, Tokyo; Naoki Takezako, Department of Hematology, National Hospital Organization National Disaster Medical Center, Tokyo; Masao Hagihara, Department of Hematology, Eiju General Hospital, Tokyo; Shinya Okuda, Department of Hematology and Oncology, JR Tokyo General Hospital, Tokyo; Naoto Tomita, Department of Internal Medicine and Clinical Immunology, Yokohama City University Hospital, Yokohama; Tomonori Nakazato, Department of Hematology, Yokohama Municipal Citizen’s Hospital, Yokohama; Akiko Negoro, Department of Hematology, Japan Labor Health and Welfare Organization Yokohama Rosai Hospital, Yokohama; Takaaki Chou, Department of Medicine, Niigata Cancer Center Hospital, Niigata; Junji Ito, Department of Clinical Laboratory, Nagoya City Midori General Hospital; Nagoya; Hiroshi Kosugi, Department of Hematology, Ogaki Municipal Hospital, Ogaki; Hiroyuki Takamatsu, Department of Hematology, Kanazawa University Graduate School of Medical Science, Kanazawa; Hiroyuki Takamatsu, Department of Hematology, NTT WEST Kanazawa Hospital, Kanazawa; Tatsuharu Ohno, Division of Hematology and Immunology, Department of Internal Medicine, Ohtsu Red Cross Hospital, Ohtsu; Junya Kuroda, Department of Hematology and Oncology, Kyoto Prefectural University of Medicine, Kyoto; Chihiro Shimazaki, Department of Hematology, Japan Community Healthcare Organization Kyoto-Kuramaguchi Medical Center, Kyoto; Nobumasa Inoue, Department of Internal Medicine, National Hospital Organization Osaka Medical Center, Osaka; Toru Murayama, Department of Hematology, Hyogo Cancer Center, Akashi; Jun Konishi, Kazutaka Sunami, Department of Hematology, National Hospital Organization Okayama Medical Center, Okayama; Yoshiaki Kuroda, Department of Hematology, Hiroshima University Hospital, Hiroshima; Mitsuhiro Itagaki, Hideki Asaoku, Department of Hematology, Hiroshima Red Cross Hospital, Hiroshima; Takaaki Miyake, Department of Hematology, Shimane University Hospital, Izumo; Toshio Wakayama, Department of Hematology, Shimane Prefectural Central Hospital, Izumo; Takeshi Harada, Masahiro Abe, Department of Hematology, Tokushima University Hospital, Tokushima; Shuji Ozaki, Etsuko Sekimoto, Hironobu Shibata, Toshio Shigekiyo, Department of Hematology, Tokushima Prefectural Central Hospital, Tokushima; Toshihiro Hashimoto, Department of Internal Medicine, Tokushima Municipal Hospital, Tokushima; Yasushi Takamatsu, Division of Medical Oncology, Hematology, and Infectious Disease, Department of Internal Medicine, Fukuoka University, Fukuoka; Naokuni Uike, Department of Hematology, National Kyushu Cancer Center, Fukuoka; Hiroyuki Hata, Department of Immunology and Hematology, Faculty of Life Sciences, Graduate School of Health Sciences, Kumamoto University, Kumamoto; Naoko Harada, Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan.

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Correspondence to Shuji Ozaki.

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Dr. Kazutaka Sunami has received research funding from Ono Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Novartis Pharmaceutical Co. Ltd., and Celgene Co. Ltd. All other authors declare no conflict of interest.

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Ozaki, S., Handa, H., Saitoh, T. et al. Evaluation of the Revised International Staging System (R-ISS) in Japanese patients with multiple myeloma. Ann Hematol 98, 1703–1711 (2019).

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  • Multiple myeloma
  • International Staging System
  • Revised International Staging System
  • Novel agents
  • Autologous stem cell transplantation