Linvoseltamab (BCMA×CD3) + Bortezomib Delivers 79% ORR and 6-mo DOR 90% in Triple-Class-Exposed R/R MM

Linvoseltamab, a bispecific antibody linking BCMA and CD3, was paired with proteasome-inhibitor bortezomib in the phase 1b LINKER-MM2 dose-escalation cohort (NCT05137054). Twenty-two heavily pre-treated relapsed/refractory myeloma patients (median 3 prior lines; 86% triple-class exposed, 59% PI-refractory) received LINVO step-up to 100 mg or 200 mg weekly plus standard bortezomib for up to 8 cycles. Among 14 efficacy-evaluable patients, confirmed ORR reached 79% (PR or better; DL1 80%, DL2 78%) with a 6-month duration-of-response rate of 90% and 6-month PFS 79%. Grade 3-4 neutropenia (45%), thrombocytopenia (36%), and infections (36%) dominated toxicity; cytokine-release syndrome was all grade 1-2 (55%), and one fatal pneumonia occurred. By comparison, single-agent teclistamab posts ~63% ORR and salvage bortezomib regimens ~69% ORR with higher neuropathy burdens, underscoring the combo’s high early activity with manageable added toxicity.