Frigault MJ, Bishop MR, Rosenblatt J, et al. Phase 1 Study of CART-ddBCMA for the Treatment of Subjects With Relapsed and Refractory Multiple Myeloma. Blood Advances. 2022; (doi: 10.1182/bloodadvances.2022007210).
A novel B cell maturation antigen (BCMA)-targeting chimeric antigen receptor T-cell (CART) treatment is safe in patients with relapsed and refractory multiple myeloma (RRMM). Researchers designed the antigen to reduce immunogenicity and enhance CAR cell surface stability. The study involved 13 RRMM patients ≥18 years old, who had received at least three prior systemic therapy courses. Participants were given one dose of 100x106 CART-ddBCMA (DL1) or 300x106 CART-ddBCMA (DL2) after standard lymphodepleting chemotherapy. CART-ddBCMA was well-tolerated and had a favorable toxicity profile. The researchers observed only one case of grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, which both occurred at DL2 and could be managed using standard treatment. The maximum tolerated dose was not reached. CART-ddBCMA generated a response in all of patients, and 75% (9) had a complete response or stringent complete response. Responses intensified over time, and eight of nine (89%) evaluable patients experienced minimal residual disease negativity at median follow-up 56 weeks.