Wolfgang Miesbach: Teclistamab Targets the Source of Pathogenic Autoantibodies
Wolfgang Miesbach, Head of the Hemostasis and Hemophilia Center at Department of Medicine II, University Hospital Frankfurt, shared a post on LinkedIn about a recent article by Johannes Thaler et al., published in JTH, adding:
”Seven patients, seven complete remissions, and one case that should not have worked.
Two papers have just been published on teclistamab in autoantibody-mediated coagulation disorders.
The drug is a bispecific antibody approved in multiple myeloma: it links the patient’s own T cells to B-cell maturation antigen (BCMA) on plasma cells and mature B cells and destroys them, removing the source of the autoantibody instead of the autoantibody itself.
Thaler, Cihan Ay et al. (Vienna) treated seven patients off-label: acquired von Willebrand disease (2), acquired factor XI deficiency (2), catastrophic APS (3). All reached complete remission, first laboratory response after a median of 14 days, median follow-up 52 weeks.
Dobbelstein, Andreas Tiede et al. (Hannover) report acquired haemophilia A that had already defeated CyDRi, daratumumab and two infusions of anti-CD19 CAR-T cells. FVIII 104 IU/dl by day 14, inhibitor cleared, remission now beyond one year.
Some important aspects:
- Bleeding and thrombotic phenotypes responded alike, which points to the plasma cell as the common denominator.
- The bispecific worked where CAR-T had failed. BCMA reaches cells that CD20 and CD19 do not.
- No cell manufacturing and no apheresis slot: any centre with myeloma experience could deliver this.
Adverse events: hypogammaglobulinaemia in every patient, with open-ended immunoglobulin replacement, and mild cytokine release syndrome (grade 1, fever alone, controlled with antipyretics) in 3 of 7.
The question is no longer whether it works, but when to use it.”
Title: Teclistamab for the treatment of autoantibody-mediated coagulation disorders
Authors: Johannes Thaler, Karoline Gleixner, Lisbeth Eischer, Gabriel Kammerer, Joachim Rettl, Lisa Sailer, Christian Sillaber, Peter Quehenberger, Maria Theresa Krauth, Paul Knöbl, Cihan Ay, Hermine Agis
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