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Outcomes of relapse after teclistamab therapy in multiple myeloma

Year: 2025

Type: article

Abstract: Teclistamab is a first-in-class CD3xBCMA bispecific T-cell engager (TCE), approved by the FDA in October 2022 for the treatment of triple-class exposed relapsed/refractory multiple myeloma (RRMM) patients after ≥4 prior lines of therapy, a population that, prior to the advent of TCEs and CAR T-cell therapies, had a median overall survival (OS) of less than one year [ 1 , 2 ]. The MajestTEC-1 trial demonstrated an overall response rate (ORR) of 63% and median progression-free survival (PFS) and OS of 11.3 and 18.3 months, respectively. However, despite high rates of deep initial responses, most patients relapse, and no standard of care has been established following teclistamab failure. In this study, we report the outcomes of relapse after teclistamab therapy. We retrospectively analyzed 179 consecutive patients who completed step-up dosing and received at least one full dose of teclistamab at the University of Pennsylvania. All were triple-class exposed RRMM. Nine (5%) received 1 full dose, 10 (6%) received 2, 7 (4%) received 3, and 153 (85%) received ≥4 doses. Patients were treated either in clinical trials ( n = 55; first dose: Dec 2018–Dec 2023) or commercially ( n = 122; first dose: Dec 2022–Apr 2024) (Fig. 1a ). Data cutoff was February 15th, 2025, with a median follow-up of 21.3 (95% CI: 19.5–24.9) months from teclistamab initiation. The International Myeloma Working Group (IMWG) criteria were used for response assessment [ 3 ] and risk stratification [ 4 ]. Fig. 1: Outcomes of relapse after teclistamab therapy. a CONSORT flow diagram depicting the design of this study. b Pie chart summarizing the outcomes of 179 patients treated with teclistamab. c Pie chart summarizing the relapse patterns in 104 patients who progressed on teclistamab. d Overall survival from the time of relapse in the 104 patients who progressed after teclistamab. e Overall survival (left) and progression-free survival (right) from first salvage therapy in 67 teclistamab-treated patients who relapsed and received salvage therapy. Tick marks indicate censored data. NE denotes not estimable. f Overall response rate (≥partial response) in 67 teclistamab-treated patients who relapsed and received salvage therapy, stratified by type of salvage therapy received. g Progression-free survival from first salvage therapy in all patients who received salvage (left) and penta-exposed patients who received salvage (right), stratified by type of salvage therapy (top) and cellular therapies (i.e., CAR T-cell or T-cell engager therapy) or not (bottom). h Univariable Cox regression analysis of clinical factors associated with progression-free survival from first salvage therapy in penta-exposed patients who received salvage. Patients who received temporizing infusional chemotherapy without definitive salvage therapy were excluded. Among patients who received temporizing therapy, progression free survival was measured from the start of definitive salvage therapy. i Sankey diagram illustrating response trajectories in 19 teclistamab-treated patients who received prior BCMA-directed therapies. Full size image

Source: Blood Cancer Journal

DOI: 10.1038/s41408-025-01408-4