As of May 20, 2024, 84 pts had received BMS-986393, 26 at the RP2D. Median age was 63 years (range 39–80); 51% were male; 67% were White and 17% Black or African American. 42% had high‑risk cytogenetics (del[17p], t[4;14], and/or t[14;16]), 55% had 1q21 gain/amp, and 45% had extramedullary disease. Pts had received a median of 5 prior regimens (range 3–15); 49% had received prior BCMA‑targeted therapy, including BCMA-directed CAR T cell therapy in 38% of pts. 76% of pts had triple-refractory disease, and 35% had penta‑refractory MM.

Across all doses, treatment-related (TR) adverse events (AEs) occurred in 94% of pts; 71% had a grade (G) 3/4 TRAE, and there was 1 TRAE-related death (cytokine release syndrome [CRS]) in pts treated at 450 × 106. Overall, 69 pts (82%) had CRS (66 at G1/2); all but 1 (G5) resolved. Three pts had macrophage activation syndrome/hemophagocytic lymphohistiocytosis (all G3), none of these events occurred at the RP2D. TR neurologic AEs, including immune effector cell-associated neurotoxicity syndrome (ICANS) and other select neurotoxicities (dizziness, ataxia, neurotoxicity, dysarthria and/or nystagmus), were observed. ICANS occurred in 8 (10%) pts (2 at G3) and resolved in 7. Other select neurotoxicity occurred in 10 pts (12%); 5 (6%) at G3 (the rest G1/2); these appeared to be dose-related. On-target/off-tumor nail, skin and oral TRAEs occurred in 19%, 30%, and 31% pts, respectively. Five pts had TR weight loss (all G1/2), and treatment-emergent (TE) infections occurred in 42 (50%; 14 pts at G3/4).

After median follow-up of 14.6 months (range, 2.8–25.2 months) with 79 efficacy-evaluable pts, ORR was maintained at 87% (91% for the RP2D). Considering disease features, ORR was 84% for pts with high-risk cytogenetics (26/31), 87% for triple-class refractory disease (52/60), 79% for prior BCMA-targeting therapy (30/38), and 86% for extramedullary disease (31/36). Of pts with minimal residual disease (MRD) data and CR or better, 88% (22/25) were MRD‑negative (10−5 depth; at any time point within 3 months prior to achieving CR or better, until the time of progression or death). Of 69 responses, 33 (48%) were ongoing. Median PFS was 14.5 months (95% CI 11.8–20.8). Dose-dependent increases in cellular expansion occurred across dose levels, and all doses consistently reduced soluble BCMA levels.