Bispecific antibodies as bridging to BCMA CAR-T cell therapy for relapsed/refractory multiple myeloma.

Autor: Fandrei D; University Hospital Leipzig, Leipzig, Germany., Seiffert S; University Hospital Leipzig, Germany., Rade M; Fraunhofer Institute for Cell Therapy and Immunology IZI, Leipzig, Germany., Rieprecht S; University Hospital Leipzig, Leipzig, Germany., Gagelmann N; University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Born P; University Hospital Leipzig, Germany., Wiemers T; University Hospital Leipzig, Leipzig, Germany., Weidner H; University Hospital Leipzig, Leipzig, Germany., Kreuz M; Fraunhofer Institute for Cell Therapy and Immunology, Department of Diagnostics, Leipzig, Germany, Germany., Schassberger T; University Hospital Leipzig, Germany., Kossmann J; University Hospital Leipzig, Germany., Mangold M; University Hospital Leipzig, Germany., Furst D; University Hospital Ulm, Germany., Fischer L; University Hospital Carl Gustav Carus, Dresden, Germany., Baber R; University Hospital Leipzig, Germany., Heyn S; University Hospital Leipzig, Germany., Wang SY; University Hospital Leipzig, Germany., Bach E; University Hospital Leipzig, Germany., Hoffmann S; University Hospital Leipzig, Germany., Metzeler KH; University of Leipzig, Leipzig, Germany., Herlling M; University Hospital Leipzig, Germany., Jentzsch M; Universiy of Leipzig, Leipzig, Germany., Franke GN; Universiy of Leipzig, Leipzig, Germany., Kohl U; University Hospital Leipzig, Germany., Friedrich M; University Hospital Leipzig, Leipzig, Germany., Boldt A; University Hospital Leipzig, Germany., Reiche K; Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany., Platzbecker U; University Hospital Leipzig, Leipzig, Germany., Vucinic V; Universiy of Leipzig, Leipzig, Germany., Merz M; University Hospital Leipzig, Leipzig, Germany.
Jazyk: angličtina
Zdroj: Blood cancer discovery [Blood Cancer Discov] 2024 Oct 23. Date of Electronic Publication: 2024 Oct 23.
DOI: 10.1158/2643-3230.BCD-24-0118
Abstrakt: Establishing a strategy for sequencing of T cell redirecting therapies for relapsed/refractory multiple myeloma (RRMM) is a pressing clinical need. We longitudinally tracked the clinical and immunological impact of bispecific T cell engaging antibodies (BsAb) as bridging therapy (BT) to subsequent BCMA-directed CAR-T cell therapies in 52 RRMM patients. BsAbs were a potent and safe option for BT, achieving the highest overall response rate (100%) to BT compared to chemotherapy, anti-CD38 or anti-SLAMF7 antibody based regimens (46%). We observed early CD4+CAR+ and delayed CD8+CAR+ T cell expansion in patients receiving BsAb as BT. In vitro cytotoxicity of CAR-T cells was comparable amongst BT options. Single-cell analyses revealed increased clonality in the CD4+ and CD8+ T cell compartments in patients with previous exposure to BsAbs at leukapheresis and on day 30 after CAR-T infusion. This study demonstrates the feasibility and efficacy of BT with BsAbs for CAR-T cell therapy in RRMM.
Databáze: MEDLINE