Clinical features associated with poor response and early relapse following BCMA-directed therapies in multiple myeloma
Details
Publication Year 2024-07-23,Volume 14,Issue #1,Page 122
Journal Title
Blood Cancer Journal
Publication Type
Research article
Abstract
Three classes of BCMA-directed therapy (BDT) exist: antibody drug-conjugates (ADCs), CAR-T, and T-cell engagers (TCEs), each with distinct strengths and weaknesses. To aid clinicians in selecting between BDTs, we reviewed myeloma patients treated at Mayo Clinic with commercial or investigational BDT between 2018-2023. We identified 339 individuals (1-exposure = 297, 2-exposures = 38, 3-exposures = 4) who received 385 BDTs (ADC = 59, TCE = 134, CAR-T = 192), with median follow-up of 21-months. ADC recipients were older, with more lines of therapy (LOT), and penta-refractory disease. Compared to ADCs, CAR-T (aHR = 0.29, 95%CI = 0.20-0.43) and TCEs (aHR = 0.62, 95%CI = 0.43-0.91) had better progression-free survival (PFS) on analysis adjusted for age, the presence of extramedullary (EMD), penta-refractory disease, multi-hit high-risk cytogenetics, prior BDT, and the number of LOT in the preceding 1-year. Likewise, compared to ADCs, CAR-T (aHR = 0.28, 95%CI = 0.18-0.44) and TCEs (aHR = 0.60, 95%CI = 0.39-0.93) had superior overall survival. Prior BDT exposure negatively impacted all classes but was most striking in CAR-T, ORR 86% vs. 50% and median PFS 13-months vs. 3-months. Of relapses, 54% were extramedullary in nature, and a quarter of these cases had no history of EMD. CAR-T demonstrates superior efficacy and where feasible, should be the initial BDT. However, for patients with prior BDT or rapidly progressive disease, an alternative approach may be preferable.
Publisher
Springer Nature
Keywords
Humans; *Multiple Myeloma/therapy/mortality/drug therapy; *B-Cell Maturation Antigen/antagonists & inhibitors; Male; Female; Middle Aged; Aged; Immunotherapy, Adoptive; Adult; Immunoconjugates/therapeutic use; Aged, 80 and over; Neoplasm Recurrence, Local/therapy/drug therapy; Recurrence; Retrospective Studies
Department(s)
Clinical Haematology
Open Access at Publisher's Site
https://doi.org/10.1038/s41408-024-01081-z
Terms of Use/Rights Notice
Refer to copyright notice on published article.


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