Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment of LCAR-B38M CAR-T: At least 5-year follow-up in LEGEND-2.

person Jian-Qing Mi 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, Shanghai, China info_outline Jian-Qing Mi, Wan-Hong Zhao, Li-Juan Chen, Wei-Jun Fu, Bai-Yan Wang, Jie Xu, Jie Liu, Shi-Wei Jin, Han Zhu, Juan Du, Hua Jiang, Huabin Sun, Yehui Jia, Xiao-Hu Fan, Jian-Yong Li, Jian Hou, Zhu Chen, Wang-Gang Zhang, Ai-Li He, Sai-Juan Chen

Authors person Jian-Qing Mi 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, Shanghai, China info_outline Jian-Qing Mi, Wan-Hong Zhao, Li-Juan Chen, Wei-Jun Fu, Bai-Yan Wang, Jie Xu, Jie Liu, Shi-Wei Jin, Han Zhu, Juan Du, Hua Jiang, Huabin Sun, Yehui Jia, Xiao-Hu Fan, Jian-Yong Li, Jian Hou, Zhu Chen, Wang-Gang Zhang, Ai-Li He, Sai-Juan Chen Organizations 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, Shanghai, China, Department of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China, Department of Hematology, Jiangsu Province Hospital, First Affiliated Hospital of Nanjing Medical University, Nanjing, China, Department of Hematology, Changzheng Hospital, The Second Military Medical University, Shanghai, China, Janssen Research & Development, Raritan, NJ, Nanjing Legend Biotech Inc., Nanjing, China, Department of Hematology, Renji Hospital Affiliated With Shanghai Jiao Tong University School of Medicine, Shanghai, China Abstract Disclosures Research Funding Other Key Research and Development Plan of ShaanXi Province, Project 2018SF-002 awarded to W–H Zhao, Project 2017ZDXM-SF-25–6 (Approval No. 2018ZDXM-SF-039) awarded to A-L He, National Natural Science Foundation of China (No. 81970189) awarded to J Xu Background: LCAR-B38M CAR-T cells express a structurally differentiated CAR construct containing a 4-1BB costimulatory domain and 2 BCMA-targeting single-domain antibodies designed to confer avidity. LEGEND-2 was a first-in-human phase 1 study of LCAR-B38M conducted in China, which showed encouraging efficacy and manageable safety in 74 patients (pts) with RRMM. The US phase 1b/2 CARTITUDE-1 and Chinese phase 2 CARTIFAN-1 trials of ciltacabtagene autoleucel, which expresses the same CAR as LCAR-B38M, confirmed the efficacy observed in LEGEND-2. Here, we present ≥5-y FU data from LEGEND-2, the longest FU for any BCMA-targeted CAR-T cell therapy study. Methods: Study design was previously published. Pts underwent lymphodepletion with cyclophosphamide (cy) 300 mg/m 2 (n=66) or cy 250 mg/m 2 plus fludarabine 25 mg/m 2 (n=8) prior to receiving LCAR-B38M at a median dose of 0.51 × 10 6 (range, 0.07-2.10 × 10 6 ) CAR-positive T cells/kg in a single (n=9) or 3 split (n=65) infusions. Results: Pts were enrolled from 30 Mar 2016 to 26 Nov 2017. As of 30 Nov 2022, median FU was 65.4 mo (range, 0.4-78.8). 74 pts had received LCAR-B38M (median age, 54.5 y; 60.8% male; median [range] 3 [1-9] prior lines of therapy [LOT]; 44.6% ISS stage I; 28.4% ISS stage III; 29.7% with extramedullary disease [EMD]; 35.7% cytogenetic high risk). No new CAR-T cell-related toxicities were reported in the analysis. ORR (87.8%), CR rate (73.0%), MRD-negative CR rate (67.6%), median DOR (23 mo), and median PFS (18 mo) were mature and the same as previously reported; median OS was previously not reached. At 65.4-mo median FU, median OS was 55.8 mo, with 33 (44.6%) pts alive and 13 (17.6%) still disease-free. Compared with pts with progressive disease (PD) or who died, pts without PD were more likely to have baseline ECOG performance status (PS) 0, IgG type MM, ISS stage I MM, numerically shorter time from diagnosis, fewer prior LOT, no light chain MM, and no EMD (Table). Conclusions: At ≥5-y FU in LEGEND-2, median OS was 55.8 mo and 18% of pts with RRMM were disease-free, raising the possibility of a cure in this heavily pretreated pt population. Our data suggest that pts who are less heavily pretreated or have good functional status may experience greater benefit, potentially being cured, from LCAR-B38M CAR-T cell therapy. Clinical trial information: NCT03090659. Baseline characteristics of pts with and without PD/death. Without PD n=13 median FU, 66.8 mo (range, 61.1-76.1) With PD/Death n=61 median FU, 64.6 mo (range, 0.4-78.8) Male / female 61.5% / 38.5% 60.7% / 39.3% Median age (range), y 53 (35-68) 55 (27-74) ECOG PS 0 61.5% 36.1% MM type: IgG / light chain 76.9% / 0% 37.7% / 31.1% EMD 0% 36.1% ISS stage I 61.5% 41.0% Median time from diagnosis (range), y 3 (1-9) 4 (1-9) Median # prior LOT (range) 2 (1-6) 3 (1-9) Median dose (range), ×10 6 cells/kg 0.432 (0.16-1.58) 0.523 (0.07-2.10)

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