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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
Salvage Therapy in Multiple Myeloma With Prior T-Cell Engager Exposure: Talquetamab, Elranatamab or Teclistamab in
James Di Palma-Grisi1, David Vesole2, David Siegel2
1Hackensack University Medical Center, Hackensack, New Jersey, USA.
Abstract:
Multiple myeloma (MM) is a hematologic malignancy manifested by proliferation of clonal plasma cells leading to end-organ damage. Despite significant advancements in therapeutics, it remains incurable. Cellular therapies such as chimeric antigen receptor (CAR-T) therapy and T-cell engager (TCE) therapies have delivered high overall response rates, but almost all patients relapse and subsequent options are limited particularly in view of the increasing prevalence of prior exposure to anti-BCMA agents and immunomodulator (IMiD) therapies. Our retrospective review of 12 patients between January 2024 and December 2025 who received a combination of talquetamab, elranatamab, or teclistamab with pomalidomide found that 11 of 12 had an overall response, of whom 6 had very good partial response or better at median follow-up of 9.9 months. All 12 patients were prior exposed to pomalidomide, of whom 10 had been exposed to prior CAR-T with a median of 7 prior lines of therapy. Safety profiles were favorable: 6 patients experienced Grade 1 CRS, 7 experienced Grade III neutropenia, and 7 of 8 patients receiving talquetamab experienced on-target, off-tumor side effects like dysgeusia and skin dryness.
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