Sequential BCMA CAR-T Cell Therapy in Refractory Multiple Myeloma Open Access

• Sequential treatment with commercially available BCMA-directed CAR-T therapy in refractory myeloma is safe and efficacious

• Duration of response to initial BCMA-directed CAR-T treatment is predictive for durable responses after sequential treatment

Multiple myeloma (MM) relapsing after BCMA-directed chimeric antigen receptor T-cell (CAR-T) treatment remains a therapeutic challenge. Data on re-exposure to CAR-T targeting the same antigen are scarce. We analyzed 10 heavily pretreated MM patients at three medical centers treated with the commercially approved CAR-T product ide-cel in a real-world setting. Upon relapse, all patients received cilta-cel as a second CAR-T infusion, with bridging treatments permitted between both therapies. Sequential therapy with BCMA-directed CAR-T therapy was safe, with no higher-grade immune cell-associated side effects or new safety signals. We found robust CAR-T expansion and high response rates (100% ³ VGPR with 60% achieving MRD-negativity) with an estimated progression-free survival 64.8% (95% CI: 39-100%) at 6 months after the second CAR-T treatment. Duration of response to first CAR-T therapy was predictive for durable responses to the second CAR-T product. Loss of BCMA antigen occurred in only one of three patients relapsing after cilta-cel. Two of three relapsing patients died within a year and showed no further response to bispecific antibody treatment. This study provides the first real-world evidence that sequential treatment with two different commercially approved BCMA CAR-T products is both feasible and effective, particularly in patients with prolonged responses to initial BCMA CAR-T therapy.