Phase II Study of BCMA Chimeric Antigen Receptor T-Cell Therapy in Patients With Newly Diagnosed Multiple Myeloma Ineligible for or Not Proceeding to Autologous Stem-Cell Transplantation (CAREMM-001).

Phase II single-arm trial of frontline BCMA CAR-T in transplant-ineligible NDMM

Design:

• Population: Newly diagnosed multiple myeloma patients ineligible for, or not proceeding to, autologous stem-cell transplant; 40 enrolled, 36 infused. Median age 68 (range 46–75).
• Treatment: 3–4 cycles of investigator-choice induction, then BCMA-directed CAR-T infusion, followed by consolidation and lenalidomide maintenance.
• Primary endpoint: MRD negativity at 10⁻⁵ sensitivity at 3 months post-infusion.

Efficacy:

• MRD negativity at 3 months: 100% (36/36; 95% CI 90.3–100.0).
• Follow-up: Median 15.8 months post-infusion (range 4.3–26.0); no MRD recurrence observed.
• Complete response rate (CRR):
  • Pre-infusion: 33.3% (12/36; 95% CI 18.6–51.0)
  • 3 months: 69.4% (25/36; 95% CI 51.9–83.7)
  • Last follow-up: 94.4% (34/36; 95% CI 81.3–99.3)
• Disease outcomes: No disease progressions or deaths reported at data cutoff.

Safety:

• Most common grade 3–4 toxicities: transient cytopenias
  • Lymphopenia: 100%
  • Neutropenia: 88.9%
  • Leukopenia: 80.6%
  • Thrombocytopenia: 19.4%
  • Anemia: 8.3%
• Cytokine release syndrome (CRS): 52.8%, all grade 1–2.
• ICANS: 5.6%, all grade 1.
• Infections: 30.6%; grade ≥3 in 19.4%.

Interpretation:

Early-line BCMA CAR-T, layered onto induction and followed by consolidation and lenalidomide maintenance, produced universal MRD negativity at 3 months and very high, deep response rates with no observed progression at ~16 months’ median follow-up in transplant-ineligible NDMM, with toxicities largely consistent with known CAR-T risks and mostly low-grade CRS/ICANS. Results support further evaluation as a potentially practice-changing frontline option in this population.