Clinical features associated with poor response and early relapse following BCMA-directed therapies in multiple myeloma

Rees, MJ; Mammadzadeh, A; Bolarinwa, A; Elhaj, ME; Bohra, A; Bansal, R; Ailawadhi, S; Parrondo, R; Chhabra, S; Khot, A; Hayman, S; Dispenzieri, A; Buadi, F; Dingli, D; Warsame, R; Kapoor, P; Gertz, MA; Muchtar, E; Kourelis, T; Gonsalves, W; Rajkumar, SV; Lin, Y; Kumar, S

Author(s): Rees, MJ; Mammadzadeh, A; Bolarinwa, A; Elhaj, ME; Bohra, A; Bansal, R; Ailawadhi, S; Parrondo, R; Chhabra, S; Khot, A; Hayman, S; Dispenzieri, A; Buadi, F; Dingli, D; Warsame, R; Kapoor, P; Gertz, MA; Muchtar, E; Kourelis, T; Gonsalves, W; Rajkumar, SV; Lin, Y; Kumar, S;
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
Publisher's Version: https://doi.org/10.1038/s41408-024-01081-z
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.

Creation Date: 2024-09-03 05:21:08

Last Modified: 2024-09-03 05:25:14