Cilta-cel (BCMA CAR-T) drives 100% MRD(10⁻⁶) negativity by 2 months in high-risk SMM

Ciltacabtagene autoleucel (cilta-cel) is a BCMA-targeted autologous CAR-T; in the CAR-PRISM Phase 2 trial (NCT05767359), HR-SMM patients received a single cilta-cel infusion (0.3–0.5×10⁶ or >0.5×10⁶ viable CAR+ T cells/kg) with no induction/bridging, excluding >40% marrow involvement (n=20 treated; data cutoff February 11, 2026). With median follow-up 15.3 months, 100% achieved MRD negativity at 10⁻⁶ by 2 months and remained MRD-negative; among those with >6 months follow-up, 16/16 reached complete response, with no progressions or deaths—well beyond typical HR-SMM management where observation remains common, and even early lenalidomide (ECOG E3A06) is primarily a “delay progression” strategy rather than a rapid deep-response approach. Toxicity was consistent with cilta-cel: no DLTs; 90% grade 3/4 transient cytopenias, 100% grade 1/2 CRS, and non-ICANS neurologic toxicities in 7 patients (including 4 cranial nerve palsies that resolved; 3 persistent grade 1 symptoms), a neurotoxicity spectrum that’s qualitatively aligned with known cilta-cel delayed/atypical neuro events reported in CARTITUDE programs.