PMID- 34777368 OWN - NLM STAT- MEDLINE DCOM- 20220207 LR - 20220207 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - Anti-BCMA CAR-T Cell Therapy in Relapsed/Refractory Multiple Myeloma Patients With Extramedullary Disease: A Single Center Analysis of Two Clinical Trials. PG - 755866 LID - 10.3389/fimmu.2021.755866 [doi] LID - 755866 AB - BACKGROUND: The prognosis of relapsed/refractory multiple myeloma (RRMM) patients with the extramedullary disease was significantly poor. Extramedullary multiple myeloma (EMM) patients gained limited benefits from traditional drugs. Anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy seems to be a promising approach to treat RRMM patients. However, very few clinical studies are designed for EMM. Our study aimed to compare and assess the safety, efficacy, and pharmacokinetics of anti-BCMA CAR-T cell therapy in EMM and non-EMM. METHODS: The results from published anti-BCMA CAR-T clinical trials, in which raw data of EMM patients were available, were reviewed and summarized. Two trials conducted in our clinical centers were analyzed and presented with detailed data. RESULTS: According to published anti-BCMA CAR-T clinical trials, the ORR of EMM ranged from 57% to 100%, with the complete remission (CR) rate of 29% to 60%. Between February 22, 2017, and September 26, 2019, a total of 61 subjects (EMM 25; non-EMM 36) received anti-BCMA CAR-T cell infusion. The data-cutoff date was April 1, 2021. There were no statistical differences between EMM and non-EMM groups in adverse events (AEs), including cytokine release syndrome (CRS). The most common AEs of grade >/= 3 in both groups were hematologic toxicities. There was no significant difference in the objective response rate (ORR) and >/= complete remission (CR) rate between both groups. However, the >/= CR rate of the EMM group was lower than the non-EMM group receiving the fully human anti-BCMA CAR-T cell therapy (p = 0.026). The median progression-free survival (PFS) for EMM and the non-EMM group was 121 days and 361 days, respectively (p = 0.001). The median overall survival (OS) for EMM and the non-EMM group was 248 days and 1024 days, respectively (p = 0.005). The C(max) and AUC(0-28d) for EMM group were lower than non-EMM group (C(max), p = 0.016; AUC(0-28d), p = 0.016). Extramedullary disease was an independent prognostic risk factor for PFS (hazard ratio, 2.576; 95% CI, 1.343 to 4.941; p = 0.004) and OS (hazard ratio, 2.312; 95% CI, 1.165 to 4.592; p = 0.017) in RRMM patients receiving anti-BCMA CAR-T cell therapy. CONCLUSIONS: Based on our results, EMM patients could benefit from the two anti-BCMA CAR products, although they had a shorter PFS and OS compared with non-EMM patients. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn, identifier ChiCTR-OPC-16009113 and ChiCTR1800018137. CI - Copyright (c) 2021 Que, Xu, Xu, Almeida, Zhu, Wang, Wang, Liu, Jiang, Wang, Li and Zhou. FAU - Que, Yimei AU - Que Y AD - Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Xu, Menglei AU - Xu M AD - Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Xu, Yanjie AU - Xu Y AD - Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Almeida, Varlene Daniela Fernandes AU - Almeida VDF AD - Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhu, Li AU - Zhu L AD - Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China. FAU - Wang, Zhiqiong AU - Wang Z AD - Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China. FAU - Wang, Ying AU - Wang Y AD - Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China. FAU - Liu, Xian AU - Liu X AD - Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China. FAU - Jiang, Lijun AU - Jiang L AD - Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China. FAU - Wang, Di AU - Wang D AD - Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China. FAU - Li, Chunrui AU - Li C AD - Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China. FAU - Zhou, Jianfeng AU - Zhou J AD - Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China. LA - eng SI - ChiCTR/ChiCTR-OPC-16009113 SI - ChiCTR/ChiCTR1800018137 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211029 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (B-Cell Maturation Antigen) RN - 0 (Receptors, Chimeric Antigen) RN - 0 (TNFRSF17 protein, human) SB - IM MH - Adult MH - Aged MH - B-Cell Maturation Antigen/*antagonists & inhibitors MH - Clinical Trials, Phase I as Topic MH - Clinical Trials, Phase II as Topic MH - Female MH - Humans MH - Immunotherapy, Adoptive/*methods MH - Male MH - Middle Aged MH - Multiple Myeloma/mortality/*therapy MH - Neoplasm Recurrence, Local/therapy MH - Progression-Free Survival MH - Receptors, Chimeric Antigen MH - Retrospective Studies MH - *Treatment Outcome PMC - PMC8589080 OTO - NOTNLM OT - BCMA (TNFRSF17) OT - car-t OT - extramedullary OT - multiple myeloma OT - refractory OT - relapsed COIS- JZ is among the inventors of patent applications related to the novel fully human antiBCMA CAR-T (CT103A). JZ is a nonpaid member of Scientific and Medical Advisory Board of Nanjing IASO Therapeutics Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/11/16 06:00 MHDA- 2022/02/08 06:00 PMCR- 2021/01/01 CRDT- 2021/11/15 06:58 PHST- 2021/08/09 00:00 [received] PHST- 2021/10/13 00:00 [accepted] PHST- 2021/11/15 06:58 [entrez] PHST- 2021/11/16 06:00 [pubmed] PHST- 2022/02/08 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.755866 [doi] PST - epublish SO - Front Immunol. 2021 Oct 29;12:755866. doi: 10.3389/fimmu.2021.755866. eCollection 2021.