Bispecific Antibodies as Bridging to BCMA CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • David Fandrei - , Fraunhofer Institute for Cell Therapy and Immunology (Author)
  • Sabine Seiffert - , University Hospital Leipzig (Author)
  • Michael Rade - , Fraunhofer Institute for Cell Therapy and Immunology (Author)
  • Susanne Rieprecht - , University Hospital Leipzig (Author)
  • Nico Gagelmann - , University Hospital Hamburg Eppendorf (Author)
  • Patrick Born - , University Hospital Leipzig (Author)
  • Thomas Wiemers - , University Hospital Leipzig (Author)
  • Heike Weidner - , Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden (Author)
  • Markus Kreuz - , Fraunhofer Institute for Cell Therapy and Immunology (Author)
  • Tamara Schassberger - , University Hospital Leipzig (Author)
  • Jannik Koßmann - , University Hospital Leipzig (Author)
  • Marlene Mangold - , University Hospital Leipzig (Author)
  • Daniel Fürst - , German Red Cross Blood Donation Service Baden-Württemberg/Hessen, Ulm University Medical Center (Author)
  • Luise Fischer - , University Hospital Leipzig (Author)
  • Ronny Baber - , University Hospital Leipzig (Author)
  • Simone Heyn - , University Hospital Leipzig (Author)
  • Song Yau Wang - , University Hospital Leipzig (Author)
  • Enrica Bach - , University Hospital Leipzig (Author)
  • Sandra Hoffmann - , University Hospital Leipzig (Author)
  • Klaus H Metzeler - , University Hospital Leipzig (Author)
  • Marco Herling - , University Hospital Leipzig (Author)
  • Madlen Jentzsch - , University Hospital Leipzig (Author)
  • Georg-Nikolaus Franke - , University Hospital Leipzig (Author)
  • Ulrike Köhl - , University Hospital Leipzig (Author)
  • Maik Friedrich - , University Hospital Leipzig (Author)
  • Andreas Boldt - , University Hospital Leipzig (Author)
  • Kristin Reiche - , Center for Scalable Data Analytics and Artificial Intelligence (ScaDS.AI) Dresden/Leipzig (Author)
  • Uwe Platzbecker - , University Hospital Leipzig (Author)
  • Vladan Vucinic - , University Hospital Leipzig (Author)
  • Maximilian Merz - , University Hospital Leipzig (Author)

Abstract

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 immunologic impact of bispecific T cell-engaging antibodies (BsAb) as bridging therapy (BT) to subsequent B-cell maturation antigen-directed chimeric antigen receptor T (CAR-T) cell therapies in 52 patients with RRMM. BsAbs were a potent and safe option for BT, achieving the highest overall response rate (100%) to BT compared with 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 BsAbs as BT. In vitro cytotoxicity of CAR-T cells was comparable among 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 cell infusion. This study demonstrates the feasibility and efficacy of BT with BsAbs for CAR-T cell therapy in RRMM. Significance: CAR-T cell therapy and BsAbs have revolutionized treatment of triple-class refractory multiple myeloma; however, optimal sequencing is unknown. We demonstrate that BT with BsAb before B-cell maturation antigen-directed CAR-T cell therapy is safe and effective, which might have implications for other hematologic malignancies as well. See related commentary by Bal and Costa, p. 10.

Details

Original languageEnglish
Pages (from-to)38-54
Number of pages17
JournalBlood cancer discovery
Volume6
Issue number1
Publication statusPublished - 1 Jan 2025
Peer-reviewedYes

External IDs

PubMedCentral PMC11707513
Scopus 85215146701
ORCID /0009-0001-6045-3349/work/182336211

Keywords

Keywords

  • Humans, Multiple Myeloma/therapy, Antibodies, Bispecific/therapeutic use, Immunotherapy, Adoptive/methods, B-Cell Maturation Antigen/immunology, Middle Aged, Male, Female, Aged, Adult, Receptors, Chimeric Antigen/immunology, Neoplasm Recurrence, Local/therapy, T-Lymphocytes/immunology