| Abstract: |
Despite the astonishing outcomes after chimeric antigen receptor (CAR) T-cell therapy for relapsed refractory multiple myeloma (RRMM), most patients eventually relapse. There are only limited data available on salvage therapies following relapse after BCMA-directed CAR T-cell therapy. Here, we analyzed outcomes of post-CAR T-cell therapy relapse and impact of different salvage strategies in an international cohort of 139 patients (n = 130 ide-cel, n = 9 cilta-cel), receiving talquetamab (n = 28), teclistamab (n = 37), combinations of immunomodulating drugs (IMiDs), proteasome inhibitors (PIs) or CD38 monoclonal antibodies (n = 43), and others (n = 31). The median time to relapse after CAR T-cell therapy was 5 months, 53% had the extramedullary disease (EMD) at relapse, associated with dismal post-relapse outcome (P = 0.005). Overall response and complete response upon salvage therapies were 79% and 39% for talquetamab, 64% and 32% for teclistamab, 30% and 0% for IMiDs/PIs/CD38, and 26% and 3% for others (P < 0.001). Duration of response, as well as median survival, was significantly improved with bispecific antibodies (P < 0.001, respectively). Bispecific antibodies seemed to overcome the poor prognosis associated with early relapse and EMD, and were independent predictors for improved survival in multivariable analysis. In summary, these results suggest bispecific antibodies as the standard of care for relapse after CAR T-cell therapy for RRMM. © The Author(s) 2024. |
| Keywords: |
adult; controlled study; treatment outcome; treatment response; aged; aged, 80 and over; middle aged; unclassified drug; major clinical study; fludarabine; cancer recurrence; salvage therapy; drug efficacy; proteasome inhibitor; multiple myeloma; neoplasm recurrence, local; cohort analysis; cyclophosphamide; retrospective study; monoclonal antibody; immunology; tumor recurrence; immunomodulating agent; drug therapy; observational study; g protein coupled receptor; therapy; adoptive immunotherapy; immunotherapy, adoptive; multicenter study (topic); procedures; antibodies, bispecific; bispecific antibody; very elderly; humans; human; male; female; article; b cell maturation antigen; b-cell maturation antigen; chimeric antigen receptor t-cell immunotherapy; ciltacabtagene autoleucel; teclistamab; idecabtagene vicleucel; talquetamab; tnfrsf17 protein, human; g protein coupled receptor 5d; monoclonal antibody cd38
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