Phase 2 Outcomes Show Potential of Cilta-Cel in Smoldering Myeloma

Omar Nadeem, MD, of the Dana-Farber Cancer Institute, discusses the initial results of the CAR-PRISM trial (NCT05767359), which evaluated the safety and efficacy of ciltacabtagene autoleucel (cilta-cel) in patients with smoldering myeloma. The safety run-in phase, which included 6 patients, demonstrated a highly favorable safety profile with no dose-limiting toxicities observed, allowing the trial to seamlessly transition into its expansion phase. Although neurotoxicities known to be associated with cilta-cel were present, the inflammatory complications of chimeric antigen receptor (CAR) T-cell therapy were less severe.

Every patient in the study experienced only low-grade, highly manageable cytokine release syndrome (CRS), with no instances of high-grade CRS reported. Furthermore, the trial recorded zero incidents of immune effector cell-associated neurotoxicity syndrome (ICANS) or persistent hematologic toxicities, which often complicate CAR T recovery. Other serious adverse events, such as enterocolitis or secondary malignancies, were also absent from the cohort, indicating that the regimen's safety margin is robust within this population.

The efficacy data from the trial proved to be even more compelling. At a median follow-up of just over 15 months, the overall response rate reached a universal 100% among 20 patients. Remarkably, every single participant achieved minimal residual disease (MRD) negativity at the 10^-6 threshold. This ultra-deep level of response has increasingly become the clinical gold standard for measuring the long-term effectiveness of modern multiple myeloma therapies, and speaks to the potential to suppress the disease in the precursor stage.

Nadeem highlights that these deep responses occurred early in the treatment course and have remained sustained in all patients up to the data cutoff. This marks the first time a single CAR T-cell infusion has achieved this depth and durability of response across a study population with smoldering myeloma. Although long-term follow-up spanning several years is required to confirm that it can prevent progression to symptomatic multiple myeloma, the early data raise the distinct possibility that cilta-cel could serve as a potentially curative therapy.