Dr Dholaria on the Mechanism of Action of P-BCMA-ALLO1 in Multiple Myeloma

Bhagirathbhai Dholaria, MBBS, associate professor of medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, discussed the mechanism of action of P-BCMA-ALLO1, which is being evaluated in patients with relapsed/refractory multiple myeloma in a phase 1 trial (NCT04960579).

P-BCMA-ALLO1 is manufactured using healthy donor T cells, which enables the off-the-shelf product to be produced without apheresis or manufacturing delay, Dholaria began. The agent also differs from other CAR T-cell products due to the non-viral vector gene editing technology that is used, he continued. This approach allows P-BCMA-ALLO1 to be manufactured in more of a T-cell memory phenotype compared with an activated T-cell phenotype, he explained.

In the final P-BCMA-ALLO1 product, which was used in the phase 1 study, most of the cells had a CAR gene, Dholaria noted. These cells have been shown to be more effective and persistent in vivo compared with other CAR T-cell agents, he added. This design also enables P-BCMA-ALLO1 to be less toxic, with fewer instances of cytokine release syndrome (CRS) and neurotoxicity compared with other CAR T-cell products, he concluded.

Data from the study presented during the 2025 Transplantation & Cellular Therapy Meetings demonstrated that patients who received the CAR T-cell agent (n = 32) experienced an overall response rate (ORR) of 88%. Notably, the ORRs among patients who received no (n = 16) or at least 1 (n = 16) prior BCMA-targeted therapy were 100% and 75%, respectively. The ORRs for patients who received at least 1 prior BCMA-targeted bispecific antibody (n = 12) or at least 1 previous BCMA-targeted therapy and talquetamab (Talvey; n = 9) were 75% and 78%, respectively.

In the safety population (n = 36), any-grade treatment-emergent adverse effects (TEAEs) were reported in all patients; grade 3 TEAEs occurred in 89% of patients. Grade 1 to 2 CRS occurred in 42% of patients, with a median time to onset of 8 days (range, 2-12) and a median time to resolution of 11 days (range, 4-39). There were no instances of grade 3 or higher CRS.

Grade 1 to 2 immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 14% of patients. The median times to onset and resolution of ICANS were 4 days (range, 3-9) and 7 days (range, 3-10), respectively. No grade 3 or higher ICANS was reported.