Dr Dholaria on the Rationale for Investigating P-BCMA-ALLO1 in R/R Myeloma

“The purpose of this study was to determine the safety of P-BCMA-ALLO1 in patients with relapse or refractory multiple myeloma who have received 3 or 4 prior lines of therapy.”

Bhagirathbhai Dholaria, MBBS, an associate professor of medicine in the Division of Hematology Oncology at Vanderbilt University Medical Center, discussed the clinical rationale and evolving investigation of P-BCMA-ALLO1, a non-viral, allogeneic BCMA-directed CAR T-cell therapy, in patients with relapsed/refractory multiple myeloma.

Data from a phase 1 trial (NCT04960579) presented at the 2025 Transplant & Cellular Therapy Meetings demonstrated that treatment with P-BCMA-ALLO1 was safe and feasible in heavily pretreated patients, including those with prior exposure to BCMA-targeted therapies such as an autologous CAR T-cell therapy or bispecific antibody. The study employed a 3+3 dose-escalation schema and evaluated multiple cell doses across arms stratified by different lymphodepletion intensities.

Early observations indicated that standard lymphodepletion (fludarabine 30 mg/m² and cyclophosphamide 300 mg/m²) was insufficient for promoting optimal CAR T-cell expansion and antitumor activity. As a result, subsequent cohorts incorporated intensified lymphodepletion regimens using higher cyclophosphamide doses ranging from 500 mg/m2 to 1000 mg/m² alongside fludarabine, with the goal of enhancing in vivo CAR T-cell persistence.

The rationale for developing P-BCMA-ALLO1 centers on several critical unmet needs in relapsed/refractory multiple myeloma, Dholaria noted. As BCMA-targeted autologous CAR T-cell therapies and bispecific antibodies are increasingly integrated into earlier treatment lines, patients who relapse post-treatment require novel therapeutic strategies. P-BCMA-ALLO1, as an off-the-shelf, non-viral manufacturing platform, offers a potentially scalable and accessible approach, particularly for those no longer eligible for autologous options.

Dholaria emphasized that continued investigation into the safety and efficacy of P-BCMA-ALLO1 across both BCMA-naive and BCMA-experienced populations is warranted. Future analyses will further define its role in treatment sequencing and clarify whether this approach can serve as a viable salvage strategy or move earlier in the therapeutic paradigm for relapsed/refractory multiple myeloma.