Phase 2 trial of ciltcabtagene autoleucel in high-risk smoldering multiple myeloma

High-risk smoldering multiple myeloma (HR-SMM) carries an increased risk of progression to multiple myeloma. The phase 2 CAR-PRISM trial, at Dana-Farber Cancer Institute (Boston, MA) evaluated ciltcacabtagene autoleucel (cilta-cel) for HR-SMM without induction or bridging therapy Patients with > 40% marrow involvement were excluded.Primary endpoints were dose-limiting toxicities (DLTs) and treatment-emergent adverse events; secondary endpoints were response and minimal residual disease (MRD) negativity. As of 11 February 2026, 20 patients had been treated. The trial met the prespecified endpoint. No DLTs occurred. Adverse events included transient cytopenias (90% grade 3-4) and cytokine release syndrome (100% grade 1-2). Non-immune effector cell-associated neurotoxicity syndrome neurologic toxicities occurred in seven patients, with four compromising cranial nerve palsies that completely resolved. Three patients had persistent grade 1 symptoms. At a median follow-up of 15.3 months, all patients achieved MRD negativity 10^-6 by 2 months and have remained MRD negative. Sixteen patients with follow-up longer than 6 months achieved a complete response; no progression or deaths were observed. The authors conclude that cilta-cel produced rapid, deel, sustained MRD-negative responses in HR-SMM without induction therapy, whereas toxicities were consistent with the known safety profile of cilta-cel.