Sequencing T-cell redirection therapies leads to deep and durable responses in relapsed/refractory myeloma patients.

T-cell redirection therapy with chimeric antigen receptor (CAR)-T cells and bispecific antibodies (BiAbs) has shown promising efficacy in heavily pretreated relapsed/refractory multiple myeloma (RRMM) patients, leading to the approval of two CAR-T cell products and numerous BiAb trials. Data regarding outcomes after relapse following BiAbs are urgently needed to develop strategies for sequencing salvage therapies. We identified fifty-eight patients progressing after a BiAb trial at the Mount Sinai Hospital. Progression-free survival (PFS) to first- (PFS1) and second salvage therapy (PFS2), and overall survival (OS) were estimated using the Kaplan-Meier method. Patients had a median age of 67 years and 78% had high-risk cytogenetics. They had a median of 6 prior therapy lines, 89% were triple-class refractory and 44% were penta-drug refractory. After the BiAb trial, patients were followed for a median of 30.5 months and received a median of two additional salvage therapies (range: 1-9). The most common first salvage was T-cell redirection in nineteen patients (ten BiAb and nine CAR-T). Ten patients received T-cell redirection as second salvage. T-cell redirection therapy as first or second salvage was feasible and associated with a median PFS1 of 28.9 months and PFS2 of 30.9 months and an OS of 62% at 2 years. Sequential use of different T-cell redirection therapies is possible and can lead to deep and durable responses following relapse after BiAb therapy in RRMM.