Clinical Significance of Measurable Residual Disease (MRD) in Relapsed/Refractory Multiple Myeloma (RRMM) Patients (Pts) Treated with Chimeric Antigen Receptor (CAR) T Cells and T-Cell Engagers (TCE)

Background: CAR T cells and TCE are approved for the treatment of RRMM and are being investigated in newly diagnosed pts. Because their mode of action differs with respect to other drugs used in MM, the clinical significance of conventional prognostic factors must be reanalyzed in the era of newer immunotherapies. In this regard, the role of MRD remains uncertain in RRMM pts treated with CAR T cells, and virtually unknown in the setting of TCE. Aim: Analyze the clinical significance of MRD assessment in RRMM pts treated with CAR T cells and TCE. Methods: This study included 269 RRMM pts, 125 treated with CAR T cells and 144 with TCE. Most pts received anti-BCMA (n=193) and anti-GPRC5D (n=55) immunotherapies. The median follow-up was 11 months. MRD was assessed in bone marrow aspirates from 190 of the 269 RRMM patients; those without an assessment were considered as MRD positive in the intent to treat (ITT) analyses. A total of 509 longitudinal MRD studies were performed using NGF in the core laboratories of PETHEMA/GEM. The median number of MRD studies per pt was 2 (range, 1 - 7) High-risk cytogenetics included t(4;14), t(14;16) and/or del(17p). Extramedullary disease (EMD) was considered if involving soft tissues. Results: Pts treated with CAR T cells and TCE received a median number of three and four prior lines of therapy, respectively. Those infused with CAR T cells had more frequently ISS 1 (57% vs 40%, P = .02) and showed less EMD (23% vs 40%, P = .006) compared to cases treated with TCE. The incidence of high-risk cytogenetics was similar in both groups. The median PFS and OS of the ITT population since treatment initiation was 10 and 25 months, respectively. The median PFS of MRD negative (n=122, 45%) vs MRD positive (n=147, 55%) pts was 20 vs 3 months (HR: 0.11, P