Efficacy of elotuzumab for multiple myeloma deteriorates after daratumumab: a multicenter retrospective study

Naokazu Nakamura^{1

2}, Nobuyoshi Arima³, Teruhito Takakuwa⁴, Satoshi Yoshioka⁵, Kazunori Imada⁵, Kentaro Fukushima⁶, Masaaki Hotta⁷, Shin-Ichi Fuchida⁸, Junya Kanda⁹, Nobuhiko Uoshima¹⁰, Yuji Shimura¹¹, Hirokazu Tanaka¹², Kensuke Ohta¹³, Satoru Kosugi¹⁴, Hideo Yagi¹⁵, Satoshi Yoshihara¹⁶, Ryosuke Yamamura¹⁷, Yoko Adachi¹⁸, Hitoshi Hanamoto¹⁹, Hirohiko Shibayama²⁰, Naoki Hosen⁶, Tomoki Ito⁷, Chihiro Shimazaki⁸, Akifumi Takaori-Kondo⁹, Junya Kuroda¹¹, Itaru Matsumura¹², Masayuki Hino⁴; Kansai Myeloma Forum

Affiliations

¹ Department of Hematology, Shinko Hospital, 1-4-47, Wakihamacho, Chuo-Ku, Kobe, Hyogo, 651-0072, Japan. n_nakamura@kuhp.kyoto-u.ac.jp.
² Department of Hematology and Oncology Graduate School of Medicine, Kyoto University, Kyoto, Japan. n_nakamura@kuhp.kyoto-u.ac.jp.
³ Department of Hematology, Shinko Hospital, 1-4-47, Wakihamacho, Chuo-Ku, Kobe, Hyogo, 651-0072, Japan.
⁴ Department of Hematology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
⁵ Department of Hematology, Japanese Red Cross Osaka Hospital, Osaka, Japan.
⁶ Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Suita, Japan.
⁷ First Department of Internal Medicine, Kansai Medical University, Hirakata, Japan.
⁸ Department of Hematology, Japan Community Health Care Organization Kyoto Kuramaguchi Medical Center, Kyoto, Japan.
⁹ Department of Hematology and Oncology Graduate School of Medicine, Kyoto University, Kyoto, Japan.
¹⁰ Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
¹¹ Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
¹² Department of Hematology and Rheumatology, Faculty of Medicine, Kindai University, Osakasayama, Japan.
¹³ Hematology Ohta Clinic, Shinsaibashi, Japan.
¹⁴ Department of Internal Medicine (Hematology), Toyonaka Municipal Hospital, Toyonaka, Japan.
¹⁵ Department of Hematology and Oncology, Nara Prefecture General Medical Center, Nara, Japan.
¹⁶ Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
¹⁷ Department of Hematology, Osaka Saiseikai Nakatsu Hospital, Nakatsu, Japan.
¹⁸ Department of Internal Medicine, JCHO Kobe Central Hospital, Kobe, Japan.
¹⁹ Department of Hematology, Kindai University Nara Hospital, Nara, Japan.
²⁰ Department of Hematology, National Hospital Organization Osaka National Hospital, Osaka, Japan.

PMID: 38492020
DOI: 10.1007/s00277-024-05705-z

Multicenter Study

Efficacy of elotuzumab for multiple myeloma deteriorates after daratumumab: a multicenter retrospective study

Naokazu Nakamura et al. Ann Hematol. 2024 Dec.

. 2024 Dec;103(12):5681-5690.

doi: 10.1007/s00277-024-05705-z. Epub 2024 Mar 16.

Authors

Affiliations

¹ Department of Hematology, Shinko Hospital, 1-4-47, Wakihamacho, Chuo-Ku, Kobe, Hyogo, 651-0072, Japan. n_nakamura@kuhp.kyoto-u.ac.jp.
² Department of Hematology and Oncology Graduate School of Medicine, Kyoto University, Kyoto, Japan. n_nakamura@kuhp.kyoto-u.ac.jp.
³ Department of Hematology, Shinko Hospital, 1-4-47, Wakihamacho, Chuo-Ku, Kobe, Hyogo, 651-0072, Japan.
⁴ Department of Hematology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
⁵ Department of Hematology, Japanese Red Cross Osaka Hospital, Osaka, Japan.
⁶ Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Suita, Japan.
⁷ First Department of Internal Medicine, Kansai Medical University, Hirakata, Japan.
⁸ Department of Hematology, Japan Community Health Care Organization Kyoto Kuramaguchi Medical Center, Kyoto, Japan.
⁹ Department of Hematology and Oncology Graduate School of Medicine, Kyoto University, Kyoto, Japan.
¹⁰ Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
¹¹ Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
¹² Department of Hematology and Rheumatology, Faculty of Medicine, Kindai University, Osakasayama, Japan.
¹³ Hematology Ohta Clinic, Shinsaibashi, Japan.
¹⁴ Department of Internal Medicine (Hematology), Toyonaka Municipal Hospital, Toyonaka, Japan.
¹⁵ Department of Hematology and Oncology, Nara Prefecture General Medical Center, Nara, Japan.
¹⁶ Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
¹⁷ Department of Hematology, Osaka Saiseikai Nakatsu Hospital, Nakatsu, Japan.
¹⁸ Department of Internal Medicine, JCHO Kobe Central Hospital, Kobe, Japan.
¹⁹ Department of Hematology, Kindai University Nara Hospital, Nara, Japan.
²⁰ Department of Hematology, National Hospital Organization Osaka National Hospital, Osaka, Japan.

PMID: 38492020
DOI: 10.1007/s00277-024-05705-z

Abstract

Elotuzumab-based regimens are sometimes selected for multiple myeloma treatment after daratumumab-based regimens. However, there has been insufficient discussion on the efficacy of elotuzumab after daratumumab. We used Kansai Myeloma Forum registration data in a multicenter retrospective evaluation of the efficacy of elotuzumab after daratumumab. Overall survival (OS) rate and time to next treatment (TTNT) were significantly worse in the cohort given elotuzumab after daratumumab (Dara cohort, n = 47) than in the cohort with no history of daratumumab administration before elotuzumab (No-Dara cohort, n = 80, OS: P = 0.03; TTNT: P = 0.02; best response: P < 0.01). In the Dara cohort, OS and TTNT rates were worse with sequential elotuzumab use after daratumumab than with non-sequential (OS: P = 0.02; TTNT: P = 0.03). In patients given elotuzumab < 180 days after daratumumab, OS (P = 0.08) and best response (P = 0.21) tended to be worse, and TTNT was significantly worse (P = 0.01), than in those given elotuzumab after ≥ 180 days. These findings were confirmed by subgroup analyses and multivariate analyses. Monoclonal-antibody-free treatment might be preferable after daratumumab-based regimens. If possible, elotuzumab-based regimens should be considered only ≥ 180 days after daratumumab use.

Keywords: Daratumumab; Elotuzumab; Immune microenvironment; Multiple myeloma.

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Conflict of interest statement

Declarations. Ethical Approval: The study was conducted in accordance with the Declaration of Helsinki and was approved by the ethics committee of the KMF and Shinko Hospital. Competing interests: TT received honoraria from Sanofi K.K. and Janssen Pharmaceutical K.K. and grants from Bristol-Myers Squibb Co., Incyte Biosciences Japan G.K., GSK Corp. and Pfizer Japan Inc. SF received personal fees from Takeda Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K. and Sanofi K.K. JK received honoraria from Bristol-Myers Squibb Co., Janssen Pharmaceutical K.K., Takeda Pharmaceutical Co., Ltd., Sanofi K.K. and Ono Pharmaceutical Co., Ltd. and is in advisory roles at Janssen Pharmaceutical K.K, and Novartis Pharma K.K. NU received honoraria from Nippon Shinyaku Co., Ltd., Bristol-Myers Squibb Co. and Janssen Pharmaceutical K.K. KO received an honorarium from Takeda Pharmaceutical Co., Ltd. SY received honoraria from Janssen Pharmaceutical K.K. and Bristol-Myers Squibb Co. HH received honoraria from CLS Behring K.K. and Takeda Pharmaceutical Co., Ltd. HS received honoraria from Takeda Pharmaceutical Co., Ltd., Fujimoto Pharmaceutical Corp., Eisai Co., Ltd., Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Sanofi K.K., AbbVie G.K. and Novartis Pharma K.K., as well as grants from Bristol-Myers Squibb Co., Ono Pharmaceutical Co., Ltd. and AbbVie G.K. NH received personal fees from Otsuka Pharmaceutical K.K. and Chugai Pharmaceutical Co., Ltd. and grants from Chugai Pharmaceutical Co., Ltd., Teijin Pharma Corp., Kyowa Kirin Co., Eisai Co., Ltd., Ono Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., AbbVie G.K., Shionogi Pharma and Asahi Kasei Pharma Corp. TI received honoraria from Bristol-Myers Squibb Co., CSL Behring, Janssen Pharmaceutical, Novartis Pharma, Takeda Pharmaceutical Co and AbbVie G.K. CS received honoraria from Janssen Pharmaceutical K.K., Bristol-Myers Squibb Co. and Sanofi K.K. AT-K received honoraria from Nippon Shinyaku Co., Ltd., Bristol-Myers Squibb Co., Janssen Pharmaceutical K.K., Otsuka Pharmaceutical K.K. and Megakaryon Corp., as well as personal fees from Ono Pharmaceutical Co., Ltd., COGNOA Corp., and PharmaEssentia Corp. JK is a consultant for Janssen Pharmaceutical, Pfizer, AbbVie and Bristol Myers Squibb; has received research funding from Kyowa Kirin, Chugai Pharmaceutical, Asahi Kasei, Sumitomo Pharma, Otsuka Pharmaceutical, Mochida Pharmaceutical and the Japan Blood Products Organization; and has received honoraria from Janssen Pharmaceutical, Kyowa Kirin, Chugai Pharmaceutical, Ono Pharmaceutical Co., Ltd. , Sanofi. K.K., Astra Zeneca. K.K., Astellas. K.K., Eisai Co. Ltd., AbbVie G.K., Novartis, Daiichi Sankyo, Amgen, Otsuka Pharmaceutical and BMS. IM received honoraria from AstraZeneca K.K., AbbVie G.K., Otsuka Pharmaceutical K.K., Novartis Pharma K.K., Pfizer Japan Inc., Janssen Pharmaceutical K.K., Ono Pharmaceutical Co., Ltd. and Bristol-Myers Squibb Co., as well as grants from Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Taiho Pharmaceutical, AbbVie GK., Otsuka Pharmaceutical K.K., Asahi Kasei Pharma Corporation, Sumitomo Pharma Co., Ltd. and Kyowa Kirin Co. MH received honoraria from Novartis Pharma K.K., Bristol-Myers Squibb Co., Otsuka Pharmaceutical K.K. and Kyowa Kirin Co.; personal fees from LabCorp Drug Development Japan Co., Ltd.; and grants from Otsuka Pharmaceutical K.K., Kyowa Kirin Co., Sekisui Medical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd. and Taiho Pharmaceutical. The other authors have no conflicts of interest.

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Efficacy of elotuzumab for multiple myeloma deteriorates after daratumumab: a multicenter retrospective study

Affiliations

Efficacy of elotuzumab for multiple myeloma deteriorates after daratumumab: a multicenter retrospective study

Authors

Affiliations

Abstract

Conflict of interest statement

References

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LinkOut - more resources

Full Text Sources

Medical