Dr Dholaria on Future Research Directions With P-BCMA-ALLO1 in R/R Multiple Myeloma

"BCMA-relapsed myeloma is an area of unmet need in 2025. We have multiple BCMA-targeted therapies available, and these CAR T-cell therapies are moving into earlier lines of therapy, but when patients [relapse after] autologous BCMA CAR T-cell or bispecific antibody therapy, we need to have novel treatment options. P-BCMA-ALLO1 falls into the category of therapeutic agents that can potentially salvage these patients."

Bhagirathbhai Dholaria, MBBS, an associate professor of medicine in the Division of Hematology Oncology at Vanderbilt University Medical Center, discussed next steps for the investigation of the BCMA-directed, allogeneic CAR T-cell therapy P-BCMA-ALLO1 in patients with relapsed/refractory multiple myeloma.

Results from cohort C of a phase 1 study (NCT04960579) evaluating the agent in this patient population were presented during the 2025 Transplant and Cellular Therapy Meetings and showed an objective response rate (ORR) of 88% among patients (n = 32) treated with P-BCMA-ALLO1.

Based on these findings, the trial is advancing to the phase 1b dose-expansion portion, which will evaluate the therapy using the same lymphodepletion regimen as cohort C, Dholaria shared. This phase will assess P-BCMA-ALLO1 at 2 cell doses in a BCMA-targeted therapy–naive patient population—including those with relapsed/refractory multiple myeloma and triple-refractory disease—to determine whether the absence of prior BCMA-directed treatment results in improved efficacy of P-BCMA-ALLO1, he explained.

BCMA-relapsed multiple myeloma remains a critical unmet need in 2025, given the increasing use of BCMA-targeted CAR T-cell and bispecific antibody therapies in earlier lines of treatment, Dholaria asserted. Accordingly, patients who experience disease progression following autologous BCMA CAR T-cell therapy or bispecific antibody treatment require novel therapeutic approaches, he said. P-BCMA-ALLO1 represents a potential salvage option in this setting, and is an off-the-shelf, allogeneic treatment approach that could address limitations associated with autologous CAR T-cell manufacturing and accessibility, Dholaria stated. Ongoing investigation will provide further insight into the efficacy and safety profile of this agent in BCMA-directed agent–naive and –relapsed populations, he concludes.