Cilta-Cel as an Early Cellular Therapy Approach for HR-SMM
Nadeem O, Cordas dos Santos DM, Nikiforow S, et al. Ciltacabtagene Autoleucel in High-Risk Smoldering Multiple Myeloma: The CAR-PRISM Phase II Trial. Nature Medicine. 2026; (doi: 10.1038/s41591-026-04365-y).
Findings from a Phase II study suggest that ciltacabtagene autoleucel (cilta-cel), which is thought to be more effective when delivered in earlier disease states, has promise in the setting of high-risk smoldering multiple myeloma (HR-SMM), which carries an elevated risk of progression to multiple myeloma. Researchers report results from the first 20 patients receiving the BCMA-directed chimeric antigen receptor T cell therapy as part of the CAR-PRISM study. Without induction or bridging therapy, cilta-cel achieved fast, deep, and durable responses. All 20 participants registered minimal residual disease (MRD) negativity of 10-6 within 2 months of treatment and maintained MRD negativity after median follow-up of 15.3 months. Among 16 patients with follow-up of more than 6 months, all achieved complete response with no reported deaths or disease progression. Observed toxicities matched cilta-cel's safety profile, and none were dose-limiting. Treatment-emergent adverse events consisted primarily of cytokine release syndrome, which affected 100% of the sample but at a low grade of severity, and cytopenias, which affected 90% of participants but were transient in nature. The researchers note that further research may determine whether early cellular therapy is potentially curative in HR-SMM.