The impact of daratumumab pretreatment on multiple myeloma patients undergoing autologous transplantation

Yutaka Shimazu; Junya Kanda; Kazuhito Suzuki; Akinori Wada; Taku Kikuchi; Takashi Ikeda; Nobuhiro Tsukada; Akiyoshi Miwa; Mitsuhiro Itagaki; Shinichi Kako; Kaichi Nishiwaki; Shuichi Ota; Shin-Ichiro Fujiwara; Keisuke Kataoka; Noriko Doki; Masashi Sawa; Nobuhiro Hiramoto; Akinori Nishikawa; Toshi Imai; Tatsuo Ichinohe; Yoshinobu Kanda; Yoshiko Atsuta; Koji Kawamura

doi:10.1111/cas.16198

The impact of daratumumab pretreatment on multiple myeloma patients undergoing autologous transplantation

Cancer Sci. 2024 Jul;115(7):2384-2395. doi: 10.1111/cas.16198. Epub 2024 May 16.

Authors

Yutaka Shimazu^{1

2

3}, Junya Kanda¹, Kazuhito Suzuki⁴, Akinori Wada⁵, Taku Kikuchi⁶, Takashi Ikeda⁷, Nobuhiro Tsukada⁶, Akiyoshi Miwa⁸, Mitsuhiro Itagaki⁹, Shinichi Kako¹⁰, Kaichi Nishiwaki¹¹, Shuichi Ota¹², Shin-Ichiro Fujiwara¹³, Keisuke Kataoka^{14

15}, Noriko Doki¹⁶, Masashi Sawa¹⁷, Nobuhiro Hiramoto¹⁸, Akinori Nishikawa¹⁹, Toshi Imai²⁰, Tatsuo Ichinohe²¹, Yoshinobu Kanda^{10

12}, Yoshiko Atsuta^{22

23}, Koji Kawamura²⁴

Affiliations

¹ Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
² Kyoto Innovation Center for Next Generation Clinical Trials and iPS Cell Therapy, Kyoto University Hospital, Kyoto, Japan.
³ Department of Early Clinical Development, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
⁴ Division of Clinical Oncology and Hematology, Department of Internal Medicine, the Jikei University School of Medicine, Tokyo, Japan.
⁵ Department of Hematology, University of Toyama, Toyama, Japan.
⁶ Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan.
⁷ Division of Hematology and Stem Cell Transplantation, Shizuoka Cancer Center, Shizuoka, Japan.
⁸ Department of Hematology, Tokyo-kita Medical Center, Tokyo, Japan.
⁹ Department of Hematology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan.
¹⁰ Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan.
¹¹ Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University Kashiwa Hospital, Chiba, Japan.
¹² Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
¹³ Division of Hematology, Jichi Medical University, Shimotsuke, Japan.
¹⁴ Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
¹⁵ Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo, Japan.
¹⁶ Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
¹⁷ Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.
¹⁸ Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan.
¹⁹ Department of Hematology/Oncology, Wakayama Medical University, Wakayama, Japan.
²⁰ Department of Hematology and Transfusion, Kochi Health Sciences Center, Kochi, Japan.
²¹ Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
²² Japanese Data Center for Hematopoietic Cell Transplantation, Nagakute, Japan.
²³ Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagakute, Japan.
²⁴ Division of Clinical Laboratory Medicine, Department of Multidisciplinary Internal Medicine, Tottori University, Yonago, Japan.

Abstract

The anti-CD38 antibody daratumumab (Dara) has been reported to improve the prognosis of multiple myeloma (MM) patients, but its use before autologous stem cell transplantation (ASCT) remains controversial. To clarify the prognostic impact of Dara before ASCT on MM, we performed a retrospective observational analysis. We analyzed 2626 patients who underwent ASCT between 2017 and 2020. In the comparison between patients not administered Dara (Dara- group) and those administered Dara (Dara+ group), the 1-year progression-free survival (PFS) rates were 87.4% and 77.3% and the 1-year overall survival (OS) rates were 96.7% and 90.0%, respectively. In multivariate analysis, age <65 years (p = 0.015), low international staging system (ISS) stage (p < 0.001), absence of unfavorable cytogenic abnormalities (p < 0.001), no Dara use before ASCT (p = 0.037), and good treatment response before ASCT (p < 0.001) were independently associated with superior PFS. In matched pair analysis, the PFS/OS of the Dara- group were also significantly superior. For MM patients who achieved complete or very good partial response (CR/VGPR) by Dara addition before ASCT, both PFS and OS significantly improved. However, in patients who did not achieve CR/VGPR before ASCT, the PFS/OS of the Dara+ group were significantly inferior to those of the Dara- group.

Keywords: autologous stem cell transplantation; daratumumab; multiple myeloma; prognosis; response.

Publication types

Observational Study

MeSH terms

Adult
Aged
Antibodies, Monoclonal* / administration & dosage
Antibodies, Monoclonal* / therapeutic use
Female
Hematopoietic Stem Cell Transplantation / methods
Humans
Male
Middle Aged
Multiple Myeloma* / drug therapy
Multiple Myeloma* / mortality
Multiple Myeloma* / therapy
Prognosis
Progression-Free Survival
Retrospective Studies
Transplantation, Autologous*
Treatment Outcome

Substances

daratumumab
Antibodies, Monoclonal

Grants and funding

18ek0510023h0002/Japan Agency for Medical Research and Development