Phase 2 trial reports MRD-negative responses with cilta-cel in high-risk smoldering multiple myeloma
A phase 2 trial in high-risk smoldering multiple myeloma found all 20 patients treated with cilta-cel became MRD-negative within two months and remained so after 15.3 months. No disease progression, death, dose-limiting toxicities, or high-grade side effects were observed.
A single-center, phase 2 clinical trial investigating chimeric antigen receptor T-cell therapy in patients with high-risk smoldering multiple myeloma showed that all 20 patients were negative for minimal residual disease within two months of treatment and remained MRD-negative after a median of 15.3 months of follow-up. No disease progression or death was observed, and none experienced high-grade side effects.
The CAR-PRISM trial was the first to investigate CAR T-cell therapy in patients with high-risk smoldering multiple myeloma. The results were presented at the AACR Annual Meeting 2026 and were also published in Nature Medicine.
The study enrolled patients with high-risk smoldering multiple myeloma based on the 20/2/20 criteria for stratifying patients. Using these criteria, a patient is considered to have high-risk smoldering multiple myeloma if more than 20 percent of the cells in their bone marrow are precursor plasma cells, blood levels of the M-protein exceed 2 g/dL and the ratio of involved-to-uninvolved free light-chain proteins in their blood is greater than 20. Patients with additional high-risk biomarkers and 10 percent plasma cells in the bone marrow were also allowed to enroll. The study excluded patients with greater than 40 percent plasma cell infiltration in the bone marrow based on evidence that this sub-group might be more likely to experience side effects.
Twenty patients were enrolled and given one infusion of one of three doses of ciltacabtagene autoleucel (cilta-cel) after lymphodepleting conditioning chemotherapy, but no induction chemotherapy. There were no dose-limiting toxicities, and no patients experienced high grade side effects.
All patients experienced low grade cytokine release syndrome, and no patients had grade 3 or higher cytokine release syndrome. The most common adverse events were temporary hematologic toxicities, including grade 3 or 4 neutropenia. Non-ICANS neurologic toxicities occurred in seven patients: facial nerve palsy in four that resolved completely; and three patients with residual mild but improved symptoms.
Within two months of treatment, all 20 patients experienced MRD negativity, meaning there was no detection of residual myeloma cells in the bone marrow. All patients maintained MRD negativity at a median follow-up of 15.3 months. Six patients were followed for longer than 18 months and continued to experience complete responses and maintained MRD negativity.
Cilta-cel was approved by the U.S. Food and Drug Administration in 2024 as second-line treatment for relapsed multiple myeloma. The CAR T-cells target the B-cell maturation antigen protein, which is found on the surface of abnormal plasma cells.