Evidence map›Paper›PMID 41214679›Full record

ArticleJournal of translational medicine2025

Integrated clinical and single-cell profiling of BCMA CAR-T therapy in relapsed/refractory multiple myeloma.

Chuling Fang, Lixin Wang, Weiqiang Zhao, Lei Wang, Wenfa Huang, Ziren Chen, Yiran Wang, Kun Tan, Xiao Guo, Yuanyuan Xu and 10 more

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Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

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0cells of the map it votes in
3citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

20 authors.

Chuling Fang *Department of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China.ORCID 0000-0002-8381-1823
Lixin Wang *Department of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China.
Weiqiang ZhaoDepartment of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China.
Lei WangDepartment of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China.
Wenfa HuangDepartment of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China.
Ziren ChenDepartment of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China.
Yiran WangDepartment of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China.
Kun TanDepartment of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China.
Xiao GuoDepartment of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China.
Yuanyuan XuDepartment of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China.
Shuhong WangDepartment of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China.
Lijun WangDepartment of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China.
Jingqiao QiaoDepartment of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China.
Xiangyu MengDepartment of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China.
Ziqian HeDepartment of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China.
Chuan YuShenzhen University-Haoshi Cell Therapy Institute, 155 Hong Tian Rd, Bao An District, Shenzhen, 518125, China.
Junhui MeiDepartment of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China.
Hongxin WangDepartment of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China.
Yisheng LiShenzhen University-Haoshi Cell Therapy Institute, 155 Hong Tian Rd, Bao An District, Shenzhen, 518125, China. ysli@haoshibio.com.
Li YuDepartment of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen Clinical Research Center for Hematologic Disease, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1298, Shenzhen, 518055, China. yuli@szu.edu.cn.ORCID 0000-0001-6872-2665

Funding

Chinese National Major Project for New Drug Innovation 2019ZX09201002003HaiYa Young Scientist Foundation of Shenzhen University General Hospital HY002National Natural Science Foundation of China 82030076, 82070161, 81970151, 81670162 and 81870134Natural Science Foundation of Shenzhen University General Hospital SUGH2019QD012Sanming Project of Medicine in Shenzhen SZSM202111004Shenzhen Clinical Research Center for hematologic disease LCYSSQ20220823091401002Shenzhen Key Laboratory ZDSYS20200811143757022Shenzhen Medical Research Fund C2301003Shenzhen Natural Science Fund 20200830182623001Shenzhen Science and Technology Foundation JCYJ20190808163601776, JCYJ20200109113810154
6 · The paper itself

Abstract

backgroundDespite therapeutic advances, multiple myeloma (MM) remains incurable, especially in relapsed/refractory (R/R) disease. B-cell maturation antigen (BCMA)-targeted CAR-T therapy, exemplified by FDA-approved agents like ide-cel and cilta-cel, offers promise, yet accessibility barriers necessitate local production.

methodsThis single-arm trial evaluated safety/efficacy of autologous BCMA CAR-T cells in six R/R MM patients.

resultsCytokine release syndrome (CRS) occurred in 83% (grade 1), managed with tocilizumab without neurotoxicity. Toxicities were transient and resolved. Serum cytokine (IFN-γ, IL-6/8/10) peaked during CRS. Responses included 83% overall response (67% stringent complete response), unaffected by extramedullary disease or high-risk cytogenetics. Median PFS/OS were unreached, with an estimated 12-month OS rate of 83.33% and PFS rate of 66.67%. CAR-T cell persistence, with a median Cmax at 20.5 days, remained detectable in 83% at 1 month and 67% at 6 months. Single-cell RNA sequencing (scRNA-seq) and T-cell receptor sequencing (TCR-seq) demonstrated complementary roles of functionally specialized CD8⁺ Te subsets. Clonal evolution in the sustained responder (patient 2) revealed a shift from a polyclonal infusion product (IP) to oligoclonal dominance, with shared clones exhibiting enhanced cytotoxic and NK-like activity. Transcriptional adaptation of persistent clones over time indicated distinct phases of proliferation, stress response, and long-term persistence, with a concomitant shift in cellular phenotype from IP-derived Tem/circling T cells to a mixed Tem/Te_1/Te_2 population. Comparative analysis of two patients with divergent clinical outcomes (sustained remission vs. transient remission) revealed that early CAR-T exhaustion and increased regulatory T cells (Tregs) were associated with relapse.

conclusionsLocally produced BCMA CAR-T is safe and effective in heavily pretreated R/R MM, inducing deep responses. scRNA-seq/TCR-seq findings highlight interplay of CAR-T heterogeneity, clonal adaptability, and immune regulation. CD8⁺ subset specialization and clonal persistence matter for durable responses; exhaustion and immunosuppression may cause relapse.

Indexed as

B-Cell Maturation AntigenImmunotherapy, AdoptiveMultiple MyelomaNeoplasm Recurrence, LocalReceptors, Chimeric AntigenSingle-Cell AnalysisAgedCytokinesFemaleHumansMaleMiddle AgedRecurrenceTreatment OutcomeB-Cell Maturation AntigenCytokinesReceptors, Chimeric AntigenCAR-TEfficacyRelapsed or refractory multiple myelomaSafetySingle-cell profiling

Identifiers

PMID41214679
PMCPMC12604393

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.