CAR T-Cell Therapy Shows Remarkable Early Results in High-Risk Smoldering Myeloma
On April 20, 2026, results from the single-center, phase 2 CAR-PRISM clinical trial were presented at the AACR Annual Meeting 2026 in San Diego, California. The trial investigated the CAR T-cell therapy ciltacabtagene autoleucel (cilta-cel) in 20 patients with high-risk smoldering multiple myeloma. The results were also published in Nature Medicine.
Key Trial Results
Within two months of treatment, all 20 patients were negative for minimal residual disease (MRD).
All patients remained MRD-negative after a median follow-up of 15.3 months. No disease progression or death was observed during the follow-up period. Six patients followed for longer than 18 months continued to experience complete responses and maintained MRD negativity.
Safety Profile
No patients experienced high-grade side effects. All patients experienced low-grade cytokine release syndrome (CRS). The most common adverse events were temporary hematologic toxicities, including grade 3 or 4 neutropenia. Non-ICANS neurologic toxicities occurred in seven patients. There were no dose-limiting toxicities.
Study Background and Design
Smoldering multiple myeloma is a precursor to multiple myeloma, a cancer of the bone marrow plasma cells. Approximately 50% of patients with high-risk smoldering multiple myeloma progress to active multiple myeloma within two years.
The CAR T-cell therapy cilta-cel targets the B-cell maturation antigen (BCMA) protein on abnormal plasma cells. It was approved by the FDA in 2024 as a second-line treatment for relapsed multiple myeloma.
The CAR-PRISM study investigated using this therapy earlier in the disease course, before patients transition to full multiple myeloma or are exposed to other therapies.
Patients were enrolled based on high-risk criteria, including bone marrow plasma cell percentage, M-protein levels, and free light-chain ratios. Patients with greater than 40% plasma cell infiltration were excluded. Patients received one infusion of one of three doses of cilta-cel after lymphodepleting conditioning chemotherapy, but no induction chemotherapy.
Researcher Insights
"Within two months, all patients were MRD-negative at the deepest measurable level and remained so at approximately 15 months of follow-up," stated Dr. Omar Nadeem. "This is the first time such a result has been reported in any spectrum of myeloma and it shows the efficacy of CAR T-cells in an earlier disease state."
Dr. Irene M. Ghobrial noted the hypothesis was that CAR T-cell therapy might work better when patients have a lower tumor burden and a functional immune system, with the goal of learning if it can provide deep, lasting remissions.
Dr. David Cordas dos Santos added, "A question is whether CAR T-cell therapy works differently in high-risk smoldering myeloma than in relapsed multiple myeloma. Studying these differences may help understand why responses appear deep and rapid in these patients."
Dr. Nadeem also stated the hope is that responses continue to be durable long-term and that CAR T-cell therapy has the potential to be a one-time treatment offering disease eradication.
Context and Future Directions
Currently, most patients with smoldering multiple myeloma are monitored and treated only upon signs of progression. In November 2025, the FDA approved daratumumab for the treatment of high-risk smoldering multiple myeloma, marking the first approved therapeutic for the disorder.
The research team plans to continue investigating CAR T-cell therapies and other immunotherapies, such as bispecific antibodies, for patients with high-risk smoldering multiple myeloma.
The study was supported by Johnson & Johnson.
About Dana-Farber Cancer Institute
Dana-Farber Cancer Institute is a cancer research and treatment center, a federally designated Comprehensive Cancer Center, and a teaching affiliate of Harvard Medical School.