A phase 2 trial, CAR-PRISM, suggests that early use of CAR T cell therapy may achieve deep and sustained responses in patients with high-risk smouldering multiple myeloma (HR-SMM), supporting the concept of disease interception before progression to symptomatic myeloma. Results from CAR-PRISM were presented at the American Association for Cancer Research (AACR) Annual Meeting 2026, held April 17-22, 2026.
HR-SMM is associated with a substantial risk of progression to overt multiple myeloma with end-organ damage, making it an important setting for early therapeutic intervention. While current strategies can delay progression, achieving durable, treatment-free remission has remained challenging.
In this phase 2 study, investigators evaluated the BCMA-directed CAR T therapy ciltacabtagene autoleucel (cilta-cel) in patients with HR-SMM, without the use of induction or bridging therapy.
CLINICAL SUMMARY
What was examined
Phase 2 study of BCMA-directed CAR T cell therapy (ciltacabtagene autoleucel) in patients with high-risk smouldering multiple myeloma.
Key findings
- All evaluable patients achieved MRD negativity (10⁻⁶) within two months, with sustained responses at a median of 15.3 months.
- High rates of complete response were observed, with no progression or deaths reported at the time of analysis.
- Toxicities were consistent with the known CAR T safety profile, including low-grade cytokine release syndrome and transient cytopenias.
Clinical implications
- Supports exploration of CAR T therapy earlier in the disease course, before symptomatic myeloma
- Suggests potential for deep and durable responses in a precursor disease setting
- Longer follow-up and larger studies are needed to confirm durability, safety, and the potential role in long-term disease control.
Twenty patients were treated, and the study met its primary safety endpoints, with no dose-limiting toxicities observed. Adverse events were consistent with the known safety profile of CAR T therapy, including predominantly low-grade cytokine release syndrome and transient cytopenias, consistent with prior experience.
Efficacy signals were strong. All evaluable patients achieved minimal residual disease (MRD) negativity at a sensitivity of 10⁻⁶ within two months, and responses were sustained at a median follow-up of 15.3 months. Among those with longer follow-up, the majority achieved complete response, with no disease progression or deaths reported at the time of analysis.
Featured Event
These findings support the concept that earlier use of cellular therapy—when tumour burden is lower and immune function better preserved—may enhance treatment efficacy. The authors suggest this approach may support exploration of curative-intent strategies in precursor disease states.
However, the small sample size and limited follow-up mean longer-term durability, safety, and broader applicability remain to be established.
From a clinical perspective, the study adds to growing interest in early intervention for high-risk precursor myeloma and highlights CAR T therapy as a potential option beyond the relapsed/refractory setting.
Paper: Nadeem, O., Cordas dos Santos, D.M., Nikiforow, S. et al. Ciltacabtagene autoleucel in high-risk smoldering multiple myeloma: the CAR-PRISM phase 2 trial. Nat Med (2026). Access online here.
