Clinical scores to predict toxicities and outcomes in patients with multiple myeloma undergoing bispecific T-cell engager therapy
The significant clinical benefit of bispecific T-cell engagers (TCEs) for the treatment of relapsed/refractory multiple myeloma (RRMM) may be offset by serious toxicities and treatment failure. Risk scores such as the CAR-HEMATOTOX (HTX), Endothelial Activation and Stress Index (EASIX) and modified EASIX (m-EASIX) can identify patients at risk for complications before CAR T-cell therapy, but their utility prior to TCE therapy remains elusive. We analyzed associations with outcomes and toxicities in independent discovery (n=123) and validation (n=155) cohorts treated with TCEs. Patients with HTX ≥ 3 or m-EASIX > median (> 0.86) had a significantly increased risk of prolonged hospitalization, antibiotic treatment and fever during step-up dosing. We also observed associations with cytopenias requiring therapeutic intervention, higher severe infection and intervention densities, as well as inferior response rates and reduced progression-free and overall survival. Our findings highlight the potential of these clinical scores to improve risk stratification before TCE therapy.
Authors
- Lisa Leypoldt (ORCID: https://orcid.org/0000-0002-9248-588X)
- David Sedloev
- Maximilian Steinhardt (ORCID: https://orcid.org/0000-0003-3644-9187)
- Jan Hendrik Frenking
- Christine Riedhammer (ORCID: https://orcid.org/0009-0008-7106-7217)
- T. G. Richardson
- Raphael Teipel (ORCID: https://orcid.org/0000-0002-9985-6583)
- Philipp Weis
- Mirco Friedrich (ORCID: https://orcid.org/0000-0002-6401-3623)
- Johannes M. Waldschmidt (ORCID: https://orcid.org/0000-0001-5340-1818)
- Julia Mersi (ORCID: https://orcid.org/0009-0008-7651-8080)
- Niklas Kehl (ORCID: https://orcid.org/0000-0003-4808-7857)
- Thomas Hielscher (ORCID: https://orcid.org/0000-0003-1277-310X)
- Marie Harzer (ORCID: https://orcid.org/0009-0002-0763-3823)
- Leo Rasche
- Valentine Landrin
- Carsten Müller-Tidow
- Sandra Sauer
- Christoph Schaefers
- Niels Weinhold
- Xiang Zhou
- Hermann Einsele
- Marc S. Raab
- Katja Weisel
- K Martin Kortüm
Institutions
- Broad Institute (US)
- Universität Hamburg (DE)
- German Cancer Research Center (DE)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Universitätsklinikum Würzburg (DE)
- University Hospital Cologne (DE)
- University Hospital Carl Gustav Carus (DE)
- Heidelberg University (US)
Publication Details
- Journal
- Blood Cancer Discovery
- Published
- 2026-02-13
- DOI
- https://doi.org/10.1158/2643-3230.bcd-25-0062
- Primary Topic
- Multiple Myeloma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00