Dr Dholaria on the Safety and Efficacy of P-BCMA-ALLO1 in R/R Myeloma

“We did not report any grade 3 or [higher] cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome.”

Bhagirathbhai Dholaria, MBBS, associate professor, Division of Hematology Oncology, Vanderbilt-Ingram Cancer Center, discusses findings from the phase 1 P-BCMA-ALLO1study (NCT04960579) evaluating P-BCMA-ALLO1, a non-viral, allogeneic BCMA-directed CAR T-cell therapy, in patients with relapsed/refractory multiple myeloma. The analysis presented at the 2025 Transplant and Cellular Therapy Meetings focused on results from the optimized lymphodepletion cohort (Arm C), assessing both safety and preliminary efficacy.

Arm C included patients with relapsed/refractory multiple myeloma who had received at least 3 prior lines of therapy included proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Notably, prior treatment with a BCMA-directed therapy was permitted.

The study included 32 evaluable patients in Arm C, and findings demonstrated an overall response rate (ORR) of 88%. Among specific subgroups, patients who were naive to BCMA-directed therapy (n = 16) achieved an ORR of 100% . Those who previously received one or more BCMA-targeted therapies (n = 12) experienced an ORR of 75% , and patients with prior exposure to both BCMA- and GPRC5D-directed therapies (n = 9) achieved an ORR of 78%. Notably, responses were rapid, with a median time to response of 16 days for patients across cohorts A, B, and C. In cohorts A and B, the median duration of response was 214 days; most patients in arm C had been enrolled within 6 months of data cutoff.

Safety data for P-BCMA-ALLO1 in cohort C showed that no cases of grade 3 or higher cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity syndrome (ICANS) were reported. Additionally, no patients experienced Parkinsonism, movement disorders, or hemophagocytic lymphohistiocytosis. The overall incidence of CRS was 42%, with all cases limited to grade 1 or 2. ICANS occurred in 14% of patients, but all events were grade 1 and resolved with minimal steroid intervention.