Outcomes in patients with multiple myeloma receiving salvage treatment after BCMA‐specific CAR‐T therapy: A retrospective analysis of LEGEND‐2

• Published in: British journal of haematology 2024-05, Vol.204 (5), p.1780-1789
• Main Authors: Liu, Rui, Yang, Rui, Xu, Xuezhu, Zhao, Wanhong, Wang, Fangxia, Zhang, Wanggang, Lei, Bo, Yang, Ruoyu, Wang, Yiwen, He, Aili, Wang, Jianli
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antigens; B-Cell Maturation Antigen; CAR‐T therapy; Chemotherapy; Chimeric antigen receptors; Female; Humans; Immunotherapy, Adoptive - adverse effects; Immunotherapy, Adoptive - methods; Lymphocytes T; Male; Middle Aged; Multiple myeloma; Multiple Myeloma - mortality; Multiple Myeloma - therapy; progress; Proteasome inhibitors; Proteasomes; Retrospective Studies; Salvage Therapy - methods; salvage treatment; Toxicity; Treatment Outcome
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.19340

Summary Chimeric antigen receptor T‐cell (CAR‐T) therapy targeting B‐cell maturation antigen (BCMA) has shown profound efficacy and manageable toxicity in patients with relapsed/refractory multiple myeloma (RRMM). However, determining the best course of treatment for post‐CAR‐T therapy relapse remains a significant challenge. We conducted a retrospective analysis of patients from the phase I LEGEND‐2 study (NCT03090659) enrolled at the Xi'an site, analysing the first salvage line of therapy and outcomes in patients with RRMM who progressed after receiving LCAR‐B38M CAR‐T therapy. Of 45 eligible patients, 34 (76%) had progressive disease (PD). Overall response rate (ORR) to salvage treatment was 50.0%. Median progression‐free survival (PFS) after starting salvage treatment was 16.3 months. Median PFS of patients receiving proteasome inhibitor (PI)‐based combination therapy was longer (28.2 months) than that of patients receiving a second BCMA CAR‐T (including LCAR‐B38M; 3.9 months, p = 0.0022) or chemotherapy (1.67 months, p = 0.0001). All patients with extramedullary disease at baseline (n = 11) progressed after CAR‐T therapy; ORR to salvage therapy was 25.0% and median PFS was 9.7 months. In conclusion, salvage therapy in patients with PD after receiving LCAR‐B38M CAR‐T cells produced moderate efficacy, with better outcomes for PI‐based salvage regimens.