P-BCMA-ALLO1 Is Safe and Efficacious in R/R Multiple Myeloma

P-BCMA-ALLO1 demonstrated activity with a compelling safety profile in patients with relapsed/refractory multiple myeloma, according to findings from arm C of a phase 1 trial (NCT04960579) presented at the 2025 Transplantation & Cellular Therapy Meetings.1

Patients who received the investigational off-the-shelf, allogeneic CAR T-cell therapy (n = 32) achieved an overall response rate (ORR) of 88%, including 100% in patients who had no prior BCMA-targeted therapy (n = 16) and 75% in patients who had received at least 1 prior anti-BCMA treatment (n = 16). Patients who had received prior BCMA-targeted and GPRC5D-targeted therapy (talquetamab [Talvey]; n = 9) experienced an ORR of 78%.

“The responses were quite rapid. [Nearly] every patient who responded did so at the time of first disease evaluation, which was about 2 weeks after the P-BCMA-ALLO1 infusion,” Bhagirathbhai Dholaria, MBBS, associate professor of medicine, Division of Hematology Oncology at Vanderbilt University Medical Center in Nashville, Tennessee, said during a presentation of the findings.

Safety results showed that 42% of patients in arm C (n = 36) experienced grade 1/2 cytokine release syndrome (CRS), with a median time to onset of 8 days (range, 2-12), and median time to CRS resolution of 11 days (range, 4-39). There were no cases of grade 3 or higher CRS reported. Grade 1/2 immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 14% of patients, with a median time to onset of 4 days (range, 3-9), and a median time to resolution of 7 days (range, 3-10). There were no grade 3 or higher cases of ICANS reported.

Fifty percent of patients had grade 1/2 infection and 5 had grade 3 or higher infection. There was no graft-versus-host disease observed at any study dose. Five patients experienced neurotoxicity, which was all grade 1, and there were no cases of Parkinsonism or neuropathies.

The most common grade 3 or higher treatment-emergent adverse effects included neutropenia (50%), leukopenia (44%), thrombocytopenia (36%), and anemia (39%).

There was 1 patient death on day 6 of the trial due to complications from infection, which was determined to be related to lymphodepletion not to P-BCMA-ALLO1.

Treatment and Study Background

Explaining the mechanism of P-BCMA-ALLO1, Dholaria said the treatment is “an off-the-shelf, BCMA-targeted CAR T-cell therapy. It’s a bit different than what’s currently available in the market. It is manufactured from a healthy donor T cell. About 7 healthy people were involved in this clinical trial to manufacture hundreds of batches of CAR-T which were given to the patients.”

The study is a phase 1, open-label, dose-escalation (3+3) trial in patients with relapsed/refractory multiple myeloma. Patients had to have been treated with at least 3 prior lines of therapy, including a proteasome inhibitor, immunomodulatory drug, and an anti-CD38 monoclonal antibody (triple-refractory). Prior BCMA-targeted treatment was allowed. Patients had to have an ECOG performance status (PS) of 0 or 1.

In study arm C, the lymphodepletion dose was fludarabine 30 mg/m2 and cyclophosphamide 750 mg/m2 given every 3 days. The range of P-BCMA-ALLO1 infused was 1.6-3.9 x 106 cells/kg.

The primary end point of the study was maximum tolerated dose/recommended dose for expansion. Secondary end points were anti-myeloma effect, and cell dose and lymphodepletion selection.

Overall, there were 33 patients enrolled in arm C and 32 patients received an infusion of P-BCMA-ALLO1. The median time from enrollment to the start of therapy was 1 day, and no prophylactic strategies such as steroids or tocilizumab were used. Four of the 32 patients were treated completely as outpatients.

Baseline characteristics showed that the median patient age was 64 years (range, 32-76), 53% were female, and 47% were male. The median time since diagnosis was 4.9 years (range, 0.8-15.1). Sixty-three percent of patients were White, 22% were Black, 6% were mixed race, and race was unknown for 9%. Overall, 34% of patients had an ECOG PS of 0 and 66% had an ECOG PS of 1. Forty-one percent of patients had extramedullary disease. Over half (53%) of patients had high-risk cytogenetics.

The median number of prior regimens was 6 (range, 2-15), 75% of patients had prior autologous stem cell transplantation, and no patients had received bridging therapy. Half of the patients had received prior BCMA therapy, broken down as prior BCMA bispecific only (16%); prior BCMA auto CAR-T only (6%); prior BCMA auto CAR-T and antibody-drug conjugate (ADC; 6%); prior BCMA bispecific and BCMA auto CAR-T (19%); prior BCMA bispecific, BCMA auto CAR-T, and ADC (3%); and prior BCMA and GPRC5D (28%).

Next Steps

In his concluding remarks, Dholaria said the study is “ongoing and currently enrolling patients in phase 1b utilizing the optimized arm C lymphodepletion regimen.” He also added that the FDA previously granted P-BCMA-ALLO1 Regenerative Medicine Advanced Therapy designation and Orphan Drug Designation.

Reference

1. Dholaria B, Cruz JC, Costello C. A phase 1 study of P-BCMA-ALLO1, a non-viral, allogeneic BCMA directed CAR-T in relapsed/refractory multiple myeloma (RRMM): results from optimized lymphodepletion cohort (arm C). Presented at: 2025 Transplantation and Cellular Therapy Meetings; February 12-15, 2025; Honolulu, HI. Abstract 48.