Results from the single-center, phase 2 CAR-PRISM (PRecision Intervention Smoldering Myeloma) clinical trial, which was the first to investigate chimeric antigen receptor (CAR) T-cell therapy for patients with high-risk smoldering multiple myeloma, showed that all 20 patients were minimally residual disease (MRD) negative within 2 months of treatment and remained MRD negative after a median follow-up of 15.3 months, with no naive patients. Severe side effects, according to results presented at the AACR Annual Meeting 2026, held April 17-22 in San Diego, California.
Within 2 months, all patients were MRD negative at the deepest measurable level, and all remained MRD negative at ~15 months of follow-up. This is the first time that this kind of result has been reported in any area of myeloma and truly demonstrates the efficacy of CAR T cells in early disease states. ”
Dr. Omar Nadeem, Speaker, Clinical Director, Myeloma Immune Effector Cell Therapy Program, Dana-Farber Cancer Institute
The results were also posted below natural medicine.
Smoldering multiple myeloma is a precursor to multiple myeloma, a cancer of the bone marrow that involves plasma cells. When myeloma cells accumulate in the bone marrow, they can cause bone fractures, anemia, kidney damage, and pain. Approximately 50% of patients with high-risk smoldering multiple myeloma progress to active multiple myeloma within 2 years.
The CAR T-cell therapy siltakavitagene autoleucel (cilta-cel) was approved by the U.S. Food and Drug Administration (FDA) in 2024 as a second-line treatment for relapsed multiple myeloma. CAR T cells target B cell maturation antigen (BCMA) proteins on the surface of abnormal plasma cells.
The CAR-PRISM study investigated the potential benefits of treating patients with CAR T-cell therapy earlier in disease progression, before they receive treatments that may increase the likelihood of drug resistance, and before they progress to full-blown multiple myeloma, which can compromise immune system function.
The hypothesis was that CAR T-cell therapy might work more effectively when a patient has a low tumor burden and the immune system is still fully able to function against cancer cells. We wanted to know if it could provide deep remission that lasts for a very long time. ”
Dr. Eileen M. Ghobrial, Principal Investigator and Director of the Dana-Farber Blood Cancer Early Detection and Prevention Center
This study enrolled high-risk smoldering multiple myeloma patients based on the 20/2/20 criteria to stratify patients. Using these criteria, a patient is considered to have high-risk smoldering multiple myeloma if 20 percent or more of the cells in the bone marrow are plasma progenitor cells, the blood concentration of M protein is greater than 2 g/dL, and the ratio of involved to uninvolved free light chain protein in the blood is greater than 20. Patients with additional high-risk biomarkers and 10 percent plasma cells in their bone marrow were also allowed to enroll. In this study, patients with >40% plasma cell infiltration within the bone marrow were excluded based on evidence that this subgroup is more likely to experience side effects.
Twenty patients were enrolled and received one infusion of one of three doses of cilta-cel after lymphodepleting conditioning chemotherapy, without induction chemotherapy. There were no dose-limiting toxicities, and no patients experienced severe side effects.
All patients experienced low-grade cytokine release syndrome (CRS), but no patient had grade 3 or higher CRS. The most common adverse events were transient hematologic toxicities, including grade 3 or 4 neutropenia. Non-ICANS neurotoxicity occurred in 7 patients. Four patients completely recovered from facial paralysis. Three patients remain with mild but improved symptoms.
All 20 patients showed negative MRD within 2 months of treatment. This means that no residual myeloma cells were detected within the bone marrow. All patients remained MRD negative with a median follow-up of 15.3 months. No disease progression or death was observed. Six patients were followed for more than 18 months and continued to have complete responses and remain MRD negative.
“Our hope is that these responses continue to persist long-term, until we can say the patient is cured,” Nadeem said.
The research team plans to continue investigating the potential of other immunotherapies, such as CAR T-cell therapy and bispecific antibodies, to learn more about how they may benefit high-risk smoldering multiple myeloma patients.
“One question is whether CAR T-cell therapy has different effects in high-risk smoldering myeloma and relapsed multiple myeloma,” said co-author Dr. David Cordas dos Santos, a Dana-Farber lecturer in medicine. “Studying these differences may help us understand why these patients develop responses so deeply and rapidly.”
Currently, most patients with smoldering multiple myeloma are monitored and treated only if they show signs of progression. In November 2025, the FDA approved daratumumab, a monoclonal antibody that targets CD38, for the treatment of high-risk smoldering multiple myeloma, making it the first treatment approved for patients with the disease.
“The results of the CAR-PRISM study set the stage for what is possible with CAR T-cell therapy for high-risk patients with multiple myeloma,” said Nadeem. “CAR T-cell therapy has the potential to be a one-time treatment to eradicate the disease.”
sauce:
Dana-Farber Cancer Institute
