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© 2025 Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Background

B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T-cell immunotherapy has shown promising results in the treatment of relapsed or refractory multiple myeloma (R/RMM). This study presents the updated long-term outcomes from our center.

Methods

Between July 30, 2018, and September 27, 2023, 141 patients with R/RMM who received BCMA CAR-T therapy were enrolled. Patients underwent conditioning chemotherapy with cyclophosphamide and fludarabine, followed by BCMA CAR-T cell infusion at a median dose of 2.36×106 cells/kg. The study evaluated overall response rates, long-term efficacy, safety profiles, and their associations with clinical and disease characteristics.

Results

At a median follow-up of 20.2 months, the safety profile of the therapy was manageable. Grade 3/4 cytokine release syndrome occurred in 36.2% of patients, with no cases of severe neurotoxicity reported. 1-month post-infusion, grade ≥3 anemia persisted in 39.6% of patients, while neutropenia (43.3%) and thrombocytopenia (52.2%) were observed. The objective response rate (ORR) among evaluable patients was 94.8%, with 50.7% achieving a complete response (CR). The 4-year progression-free survival and overall survival rates were 37.4% (95% CI, 29.1% to 48.1%) and 63.2% (95% CI, 54.8% to 72.8%), respectively, with survival curves showing gradual flattening over time. Patients with a history of autologous stem cell transplantation (ASCT) and those with extramedullary disease demonstrated significantly inferior efficacy and survival outcomes. Peak CAR-T cell expansion was positively correlated with ORR (p<0.001) and CR (p<0.001). Notably, patients with prior ASCT exhibited significantly lower CAR-T cell expansion compared with those without prior ASCT (p<0.001). Immunophenotypic analysis of infused CAR-T cells demonstrated impaired fitness in patients who received ASCT in the past year.

Conclusions

BCMA CAR-T therapy in patients with R/RMM results in significant and sustained responses, with a manageable safety profile on a large scale. Prior ASCT and extramedullary disease represent adverse prognostic factors. Patients with a history of ASCT demonstrate limited peak CAR-T cell expansion.

Details

Title
Long-term follow-up of BCMA CAR-T cell therapy in patients with relapsed/refractory multiple myeloma
Author
Jin, Chunxiang 1   VIAFID ORCID Logo  ; Chen, Rongrong 1 ; Fu, Shan 1 ; Zhang, Mingming 1 ; Teng, Yuanyin 1 ; Yang, Tingting 1 ; Song, Fengmei 1   VIAFID ORCID Logo  ; Feng, Jingjing 1 ; Hong, Ruimin 1 ; Cui, Jiazhen 1 ; Huang, Simao 1 ; Xu, Huijun 1 ; Zhang, Yanlei 2 ; Wei, Guoqing 1 ; Cai, Zhen 1 ; Yok-Lam Kwong 3 ; Yan Chan, Thomas Sau 3 ; Chang, Alex H 4 ; Huang, He 1   VIAFID ORCID Logo  ; Hu, Yongxian 1   VIAFID ORCID Logo 

 Bone Marrow Transplantation Center of The First Affiliated Hospital and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China 
 Shanghai YaKe Biotechnology Ltd, Shanghai, China 
 Division of Haematology, Medical Oncology and HSCT, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, Hong Kong 
 Shanghai YaKe Biotechnology Ltd, Shanghai, China; Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, Shanghai, China 
First page
e010687
Section
Immune cell therapies and immune cell engineering
Publication year
2025
Publication date
Mar 2025
Publisher
BMJ Publishing Group LTD
e-ISSN
20511426
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3182232549
Copyright
© 2025 Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.