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)

Clinical Snapshot

Key Findings

• P Value: Not explicitly reported for primary endpoint

• Effect Size: Complete response rate increased from 33.3% pre-infusion to 94.4% at last follow-up

• Primary Outcome: MRD negativity rate at 3 months: 100% (36/36 patients)

• Nnt Or Sensitivity: MRD sensitivity threshold: 10-5, no MRD recurrence observed during follow-up

• Confidence Interval: 95% CI for primary endpoint: 90.3-100.0%

Clinical Application

Requires specialised CAR-T manufacturing facilities, intensive monitoring capabilities, and experienced haematology teams Would require TGA approval and PBS listing; limited CAR-T centres in Australia may restrict access; aligns with ALLG/ABMTRR guidelines for high-risk myeloma management NDMM patients aged 46-75 years ineligible for or declining ASCT, with adequate performance status

Abstract

PURPOSE: Patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for or not proceeding to autologous stem-cell transplantation (ASCT)-often because of age or frailty-have limited opportunities to receive multiple effective lines of therapy, underscoring the need for novel frontline strategies. METHODS: In this phase II, open-label, single-arm trial (ClinicalTrials.gov identifier: NCT05860036), patients received 3-4 cycles of protocol-allowed induction, followed by B-cell maturation antigen (BCMA) CAR-T infusion, and subsequent consolidation and lenalidomide maintenance. The primary end point was the rate of minimal residual disease (MRD) negativity (10-5) at Month three postinfusion. RESULTS: Between April 4, 2023, and December 26, 2024, 43 patients were screened, 40 were enrolled, and 36 received infusion (median age, 68 years [46-75]). In the infused cohort, the MRD negativity rate at Month three postinfusion was 100% (36 of 36; 95% CI, 90.3 to 100.0). With a median follow-up of 15.8 months postinfusion (range, 4.3-26.0), no MRD recurrence was observed. The complete response rate (CRR) increased from 33.3% (12 of 36; 95% CI, 18.6 to 51.0) preinfusion to 69.4% (25 of 36; 95% CI, 51.9 to 83.7) at Month 3% and 94.4% (34 of 36; 95% CI, 81.3 to 99.3) at last follow-up. The most common grade 3 to 4 adverse events were transient cytopenia, including lymphopenia (100%), neutropenia (88.9%), leukopenia (80.6%), thrombocytopenia (19.4%), and anemia (8.3%). Cytokine release syndrome occurred in 52.8% of patients (all grade 1 to 2), immune effector cell-associated neurotoxicity in 5.6% (all grade 1), and infections in 30.6% (grade ≥3 in 19.4%). No deaths or disease progressions occurred by cutoff. CONCLUSION: Frontline BCMA CAR-T therapy induces deep, rapid, and durable remissions with a manageable safety profile in the NDMM population ineligible for or not proceeding to ASCT. These findings support its investigation as a potentially practice-changing strategy for this population.

References

1. 1.Yan, W., Du, C., Lv, R., Zou, H., Zhang, S., Yu, T., Yan, Y., Zhang, Y., Peng, S., Wang, T., Deng, S., Huang, W., Yi, S., Zou, D., Cheng, T., Wang, J., Chang, A. H., Qiu, L., & An, G. (2026). 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). Journal of Clinical Oncology. https://doi.org/10.1200/JCO-25-01969