T_SCM-predominant allogeneic anti-BCMA CAR-T therapy for relapsed/refractory multiple myeloma: preclinical...

Autologous CAR-T therapies targeting B-cell maturation antigen (BCMA) in relapsed/refractory multiple myeloma (RRMM) have demonstrated therapeutic clinical responses. Here, we present the characterization and interim Phase I data for P-BCMA-ALLO1, a T_SCM-predominant allogeneic CAR-T therapy targeting BCMA in heavily pretreated relapsed/refractory multiple myeloma. Preclinical analyses reveal a strong correlation between CD8⁺ T_SCM phenotype and in vivo potency in mouse xenograft models. In early clinical data (NCT04960579), among the 11 of 33 evaluable patients who received enhanced lymphodepletion, 82% (9/11) responded, with 63.6% (7/11) achieving very good partial response (VGPR) or better. All patients started therapy a median of 1 day after enrollment, with every patient receiving P-BCMA-ALLO1 infusion, and resulting in a 100% intent-to-treat (ITT) rate with no use of bridging therapy. CRS was reported in 21.2% (7/33) across all cohorts, all grade ≤2. The median time to peak CAR-T cell expansion (T_max) was 10 days post-infusion. Consistent with preclinical findings, CAR-T cell expansion is accompanied by differentiation from a predominantly T_SCM phenotype to a T_EM/T_EFF phenotype, with trafficking and persistence observed in bone marrow. These data suggest that a T_SCM cellular phenotype may offer significant advantages in efficacy, safety, and cellular persistence in the context of allogeneic CAR-T therapy. Clinical trial: NCT04960579.