Background/Objectives: Teclistamab is a bispecific antibody targeting BCMA and CD3, approved for relapsed/refractory multiple myeloma. It is administered continuously until progression or intolerance; however, prolonged use may increase infections and treatment burden. This study compares continuous versus fixed-duration teclistamab to determine whether treatment discontinuation after response is feasible without compromising outcomes. Methods: A multicenter retrospective study was conducted on adults with relapsed/refractory multiple myeloma treated with teclistamab between August 2022 and May 2024. Patients received step-up dosing followed by weekly administration. Those who achieved ≥VGPR and discontinued therapy due to deep response, toxicity, or preference were assigned to the fixed-duration group. Outcomes included response rates, progression-free survival (PFS), overall survival (OS), and adverse events. Results: Eighty-eight patients were included (continuous: n = 72; fixed: n = 16). The fixed group had higher complete response rates (69% vs. 44%) and shorter median time to best response (1 vs. 2 months). Median PFS was 16 months for continuous dosing versus 13 months for fixed-duration. Twelve-month PFS was similar (65% vs. 66%). Twelve-month OS was 83% vs. 81% in the continuous and fixed groups, respectively. Cytokine release syndrome and neurotoxicity rates were similar. Infections were more frequent and severe in the fixed cohort (75% any grade; 69% grade ≥ 3). Conclusions: Fixed-duration teclistamab after deep response appears feasible in appropriately selected patients, with comparable early survival outcomes to continuous treatment. Prospective studies are needed to define selection criteria, immune recovery markers, and optimal discontinuation timing.
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