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Single CAR T Infusion Clears Residual Disease in High-Risk Smoldering Myeloma Trial

Early, one-time CAR T shows promise to shift care for high-risk smoldering myeloma pending confirmation in larger trials.

Overview

  • At the AACR Annual Meeting with a Nature Medicine publication, Dana-Farber reported phase II CAR-PRISM results showing all 20 high-risk smoldering myeloma patients reached minimal residual disease negativity within two months and stayed negative at a median 15.3 months, with no progressions or deaths.
  • Safety was manageable, with only low-grade cytokine release syndrome in all patients, brief drops in blood counts, and seven non-ICANS neurologic events that included four reversible facial nerve palsies and three mild residual motor symptoms.
  • The single-center study gave one infusion of the BCMA-directed CAR T ciltacabtagene autoleucel after lymphodepleting chemotherapy, used no induction or bridging therapy, enrolled high-risk patients by 20/2/20 criteria, and excluded those with more than 40% marrow plasma cells.
  • Investigators tested earlier use of CAR T because tumor burden is lower and T cells are fitter before symptoms, a strategy that contrasts with daratumumab for high-risk smoldering myeloma approved in November 2025, which is given for up to three years and did not assess MRD.
  • Authors cautioned that the findings are preliminary due to the small, single-arm, single-institution design and short follow-up, noted Johnson & Johnson support, and called for randomized multicenter trials to confirm durability, safety, and comparative benefit.