“P-BCMA-101 is an autologous CAR-T therapeutic targeting BCMA and comprised of a high percentage of desirable stem cell memory T-cells,” said Caitlin L. Costello, MD, Moores Cancer Center, University of California, San Diego, during her presentation at the virtual 2020 ASH Annual Meeting, noting that P-BCMA-101 is designed to increase efficacy while minimizing toxicity.

A total of 43 heavily pre-treated patients were enrolled in the phase 1/2 trial investigating the safety and response of P-BCMA-101 cells in relapsed/refractory multiple myeloma by June 30, 2020. All patients had received proteasome inhibitors and immunomodulatory imide drugs.

The trial began as a dose escalation study of single infusions of P-BCMA-101 but was expanded to add cohorts of combination therapies. The gradual expansion of the stem memory T-cells (TSCM) over 2 to 3 weeks versus 3 to 7 days is believed to contribute to the excellent safety profile observed.

Consistent with the high percentage of TSCM, “circulating P-BCMA-101 cells were detected in blood by PCR, peaking at 2-3 weeks after infusion, and remaining detectable up to 1.5 years (ongoing at last follow-up),” wrote Dr Costello et al.

The most common adverse events were cytopenias/infections and ≥ grade 3 neutropenia (79%), thrombocytopenia (30%), and anemia (30%), which were expected in CAR T-cell studies with lymphodepleting chemotherapy.

Notably, 17% of patients experienced cytokine release syndrome. Based on the safety results, the trial was amended to allow for outpatient CAR-T cell administration.

The overall response rate during the initial dose escalation was 57% (n = 34). Due to indications of better response at lower doses but no definite dose response curve, the expansion cohorts are focusing on the lower end of the dose range.

Responses are ongoing in the four patients subsequently treated with novel therapeutic strategies and thus far, the safety profile has not changed.

The researchers determined the clinical data available is consistent with preclinical findings that the novel design of P-BCMA-101 can produce significant efficacy with low toxicity and be administered in an outpatient setting.

“Low doses appear highly efficacious and the modifications to manufacturing appear to have notably improved efficacy,” Dr Costello et al concluded. —Kaitlyn Manasterski

Costello Caitlin L, Cohen Adam D, Patel Krin K, et al. Phase 1/2 Study of the Safety and Response of P-BCMA-101 CAR-T Cells in Patients with Relapsed.Refractory (r/r) Multiple Myeloma (MM) (PRIME) with Novel Therapeutic Strategies. Presented at: the 62nd ASH Annual Meeting and Exposition; December 5-8, 2020; virtual. Abstract 134.