Poseida Therapeutics' P-BCMA-ALLO1, an allogeneic BCMA-directed CAR-T therapy, has demonstrated promising efficacy and a favorable safety profile in patients with relapsed/refractory multiple myeloma (MM). Interim results from an ongoing phase 1/1b clinical trial (NCT04960579), focusing on the optimized lymphodepletion cohort (Arm C), were presented at the 2025 Tandem Meetings | Transplantation & Cellular Therapy Meetings. The data suggest that P-BCMA-ALLO1 could offer a valuable treatment option for patients with limited alternatives, especially given its off-the-shelf availability.
Efficacy Results
The study included 32 evaluable patients in Arm C who had received at least three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Prior BCMA-directed therapy was permitted. The overall response rate (ORR) was 88%. Notably, patients who were BCMA-naive (n = 16) achieved a 100% ORR. Patients with prior exposure to one or more BCMA-targeted therapies (n = 12) experienced a 75% ORR, while those with prior BCMA- and GPRC5D-directed therapies (n = 9) achieved a 78% ORR. Responses were rapid, with a median time to response of 16 days across cohorts A, B, and C.
Bhagirathbhai R. Dholaria, MD, an associate professor of medicine at Vanderbilt University Medical Center and an investigator in the trial, highlighted the speed of response, noting that "Pretty much every patient who responded did so at the time of first disease evaluation, which was about 2 weeks after the P-BCMA-ALLO1 infusion."
Safety Profile
The safety data for P-BCMA-ALLO1 in cohort C revealed no cases of grade 3 or higher cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). The overall incidence of CRS was 42%, with all cases limited to grade 1 or 2 in severity. ICANS occurred in 14% of patients, but all events were grade 1 and resolved with minimal steroid intervention. No patients experienced Parkinsonism, movement disorders, or hemophagocytic lymphohistiocytosis.
According to Dr. Dholaria, "The most important take-home message in terms of the safety of the cohort is that we did not report any grade 3 or higher cytokines release syndrome (CRS) or immune-effector cell associated neurotoxicity syndrome (ICANS)."
Advantages of Allogeneic CAR-T Therapy
Unlike autologous CAR-T therapies, which require weeks of manufacturing time, P-BCMA-ALLO1 is an allogeneic product that is readily available. This eliminates the need for leukapheresis and reduces the waiting period, which can be critical for high-risk patients who may not be able to wait for autologous CAR-T cell manufacturing. "Given the fact that this is an allogenic product, it's readily available... Many of our high-risk patients are not able to wait that long, and they end up requiring bridging therapy, which none of the patients on this trial needed because P-BCMA-ALLO1 was available right away," Dr. Dholaria explained.
Study Design and Patient Population
The phase 1/1b trial is an open-label, dose-escalation study in patients with relapsed/refractory multiple myeloma who have received at least three prior lines of therapy. Arm C employed an optimized lymphodepletion regimen of fludarabine and cyclophosphamide. The primary endpoint of the study was maximum tolerated dose/recommended dose for expansion, with secondary endpoints including anti-myeloma effect and cell dose and lymphodepletion selection.
Regulatory Status and Future Directions
P-BCMA-ALLO1 has been granted Regenerative Medicine Advanced Therapy designation and Orphan Drug Designation by the FDA. The study is ongoing and currently enrolling patients in phase 1b utilizing the optimized Arm C lymphodepletion regimen.
