PMID- 35794616 OWN - NLM STAT- MEDLINE DCOM- 20220708 LR - 20220727 IS - 1756-8722 (Electronic) IS - 1756-8722 (Linking) VI - 15 IP - 1 DP - 2022 Jul 6 TI - Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2). PG - 86 LID - 10.1186/s13045-022-01301-8 [doi] LID - 86 AB - BACKGROUND: LCAR-B38M is a chimeric antigen receptor T cell product with two binding domains targeting B cell maturation antigen. Our previous reports showed a remarkable efficacy of LCAR-B38M in patients with relapsed/refractory multiple myeloma (RRMM) at a median follow-up of 2 years. Here, we report long-term safety and efficacy data from a median follow-up of 4 years. METHODS: LEGEND-2 was a phase 1, single-arm, open-label study conducted in four registered sites in China. Seventy-four participants with RRMM received LCAR-B38M treatment. Lymphodepletion was performed using cyclophosphamide or cyclophosphamide plus fludarabine. LCAR-B38M, at a median dose of 0.513 x 10(6) cells/kg, was intravenously administered either in three split infusions or in a single infusion. The primary objective was the safety of LCAR-B38M, and the secondary objective was efficacy. RESULTS: As of May 25, 2021, the median follow-up was 47.8 months. All patients experienced >/= 1 adverse events (AEs). Grade >/= 3 AEs were observed in 45/74 (60.8%) patients. Cytokine release syndrome (CRS) occurred in 68/74 (91.9%) cases; 7 (9.5%) had grade >/= 3 CRS. One patient experienced grade 1 central nervous system toxicity. The overall response rate was 87.8%. Fifty-four out of 74 (73.0%) patients achieved complete response. The median progression-free survival was 18.0 months, and the median overall survival for all patients was not reached. The median duration of response was 23.3 months. Four patients experienced viral infection more than 6 months post-infusion, and four patients developed second primary non-hematological malignancies at a median time of 11.5 months post-CAR-T cell transfer. CONCLUSIONS: The 4-year follow-up data of LCAR-B38M therapy demonstrated a favorable long-term safety profile and a durable response in patients with RRMM. Trial registration Clinicaltrials.gov NCT03090659 (retrospectively registered on March 27, 2017); ChiCTR-ONH-17012285. CI - (c) 2022. The Author(s). FAU - Zhao, Wan-Hong AU - Zhao WH AD - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. FAU - Wang, Bai-Yan AU - Wang BY AD - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. FAU - Chen, Li-Juan AU - Chen LJ AD - Department of Hematology, Jiangsu Province Hospital, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. FAU - Fu, Wei-Jun AU - Fu WJ AD - Department of Hematology, Changzheng Hospital, The Second Military Medical University, Shanghai, 200003, China. AD - Department of Hematology, School of Medicine, Shanghai Fourth People's Hospital, Tongji University, Shanghai, 200434, China. FAU - Xu, Jie AU - Xu J AD - State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Shanghai Institute of Hematology, Ruijin Hospital Affiliated With Shanghai Jiao Tong University School of Medicine, 197 Rui Jin er Road, Shanghai, 200025, China. FAU - Liu, Jie AU - Liu J AD - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. FAU - Jin, Shi-Wei AU - Jin SW AD - State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Shanghai Institute of Hematology, Ruijin Hospital Affiliated With Shanghai Jiao Tong University School of Medicine, 197 Rui Jin er Road, Shanghai, 200025, China. FAU - Chen, Yin-Xia AU - Chen YX AD - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. FAU - Cao, Xing-Mei AU - Cao XM AD - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. FAU - Yang, Yun AU - Yang Y AD - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. FAU - Zhang, Yi-Lin AU - Zhang YL AD - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. FAU - Wang, Fang-Xia AU - Wang FX AD - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. FAU - Zhang, Peng-Yu AU - Zhang PY AD - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. FAU - Lei, Bo AU - Lei B AD - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. FAU - Gu, Liu-Fang AU - Gu LF AD - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. FAU - Wang, Jian-Li AU - Wang JL AD - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. FAU - Zhang, Hui AU - Zhang H AD - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. FAU - Bai, Ju AU - Bai J AD - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. FAU - Xu, Yan AU - Xu Y AD - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. FAU - Zhu, Han AU - Zhu H AD - Department of Hematology, Jiangsu Province Hospital, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. FAU - Du, Juan AU - Du J AD - Department of Hematology, Changzheng Hospital, The Second Military Medical University, Shanghai, 200003, China. FAU - Jiang, Hua AU - Jiang H AD - Department of Hematology, Changzheng Hospital, The Second Military Medical University, Shanghai, 200003, China. FAU - Fan, Xiao-Hu AU - Fan XH AD - Nanjing Legend Biotech Inc., Nanjing, 210000, China. FAU - Li, Jian-Yong AU - Li JY AD - Department of Hematology, Jiangsu Province Hospital, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. FAU - Hou, Jian AU - Hou J AD - Department of Hematology, Renji Hospital Affiliated With Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China. FAU - Chen, Zhu AU - Chen Z AD - State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Shanghai Institute of Hematology, Ruijin Hospital Affiliated With Shanghai Jiao Tong University School of Medicine, 197 Rui Jin er Road, Shanghai, 200025, China. FAU - Zhang, Wang-Gang AU - Zhang WG AD - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. FAU - Mi, Jian-Qing AU - Mi JQ AD - State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Shanghai Institute of Hematology, Ruijin Hospital Affiliated With Shanghai Jiao Tong University School of Medicine, 197 Rui Jin er Road, Shanghai, 200025, China. jianqingmi@shsmu.edu.cn. FAU - Chen, Sai-Juan AU - Chen SJ AD - State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Shanghai Institute of Hematology, Ruijin Hospital Affiliated With Shanghai Jiao Tong University School of Medicine, 197 Rui Jin er Road, Shanghai, 200025, China. sjchen@stn.sh.cn. FAU - He, Ai-Li AU - He AL AD - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. heaili@xjtu.edu.cn. AD - Department of Hematology and National-Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. heaili@xjtu.edu.cn. LA - eng SI - ClinicalTrials.gov/NCT03090659 GR - 2018SF-002/Key Research and Development Plan of ShaanXi Province/ GR - 2017ZDXM-SF-25-6/Key Research and Development Plan of ShaanXi Province/ GR - 81970189/National Natural Science Foundation of China/ PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20220706 PL - England TA - J Hematol Oncol JT - Journal of hematology & oncology JID - 101468937 RN - 0 (B-Cell Maturation Antigen) RN - 8N3DW7272P (Cyclophosphamide) SB - IM MH - B-Cell Maturation Antigen MH - China/epidemiology MH - Cyclophosphamide/therapeutic use MH - Cytokine Release Syndrome MH - Follow-Up Studies MH - Humans MH - *Lymphoma, Follicular MH - *Multiple Myeloma/drug therapy MH - *Neoplasms, Second Primary PMC - PMC9261106 OTO - NOTNLM OT - B cell maturation antigen OT - Chimeric antigen receptor therapy OT - Efficacy OT - Multiple myeloma OT - Safety COIS- X-HF is employed by Legend Biotech. All other authors declare that they have no competing interests. EDAT- 2022/07/07 06:00 MHDA- 2022/07/09 06:00 PMCR- 2022/07/06 CRDT- 2022/07/06 23:48 PHST- 2022/03/11 00:00 [received] PHST- 2022/06/03 00:00 [accepted] PHST- 2022/07/06 23:48 [entrez] PHST- 2022/07/07 06:00 [pubmed] PHST- 2022/07/09 06:00 [medline] PHST- 2022/07/06 00:00 [pmc-release] AID - 10.1186/s13045-022-01301-8 [pii] AID - 1301 [pii] AID - 10.1186/s13045-022-01301-8 [doi] PST - epublish SO - J Hematol Oncol. 2022 Jul 6;15(1):86. doi: 10.1186/s13045-022-01301-8.