Outcomes of bispecific antibody therapy after CAR T-cell failure in relapsed/refractory large B-cell lymphoma

Patients with large B-cell lymphoma (LBCL) who experience relapsed disease after CD19-directed chimeric antigen receptor (CAR) T-cell (CAR-T) therapy have a poor prognosis. Bispecific antibodies (BsAbs) induce complete remissions in ∼35% of these cases. Hypothesizing overlapping LBCL-intrinsic resistance mechanisms as well as common poor prognosis predictors to CAR-T and BsAb therapy, we conducted a multicenter retrospective analysis including 92 patients with relapsed/refractory (R/R) LBCL treated with BsAbs after CAR-T failure. Overall response rate (ORR) was 43%, with a progression-free survival (PFS) of 2.8 months. Patients receiving BsAbs during early relapse (≤3 months) achieved a significantly worse outcome (ORR, 29%; PFS, 2.2 months) compared with patients with an intermediate (4-6 months; ORR, 54%; PFS, 3.7 months) or a late relapse (>6 months; ORR, 60%; PFS, 10.5 months). The benefit of later relapse was particularly notable in patients receiving BsAbs as first salvage therapy compared with those receiving a BsAb in subsequent lines (PFS not reached vs 2.7 months; overall survival not reached vs 9.1 months, respectively). In addition to early R/R state before BsAbs, elevated lactate dehydrogenase and higher International Prognostic Index score were significant predictors of poor outcomes to BsAb in multivariate Cox regression analyses. The finding that patients with early relapse after CAR-T respond particularly poorly to BsAb highlights the necessity for alternative treatment options in this high-risk patient cohort.

Authors

Institutions

Publication Details

Journal
Blood Advances
Published
2025-04-16
DOI
https://doi.org/10.1182/bloodadvances.2024015719
Citations
18
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
18.82

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Outcomes of bispecific antibody therapy after CAR T-cell failure in relapsed/refractory large B-cell lymphoma

Niklas Gebauer, Enver Aydilek, Gerald Wulf, Giuliano Filippini Velázquez et al.
18 citations
Blood Advances
CAR-T cell therapy research
18.82
article

Outcomes of bispecific antibody therapy after CAR T-cell failure in relapsed/refractory large B-cell lymphoma

Niklas Gebauer, Enver Aydilek, Gerald Wulf, Giuliano Filippini Velázquez, Fabian Müller, Georg Lenz, Paolo Mazzeo, Bastian von Tresckow, Vladan Vučinić, Ulf Schnetzke, Thomas Pabst, Rebecca Wurm‐Kuczera, Susanne Ghandili, Alexander Sebastian Hölscher, Christoph Schmid, Vadim Lesan, Thomas Weber, Sascha Dietrich, Mathias Hänel, Andreas Viardot, Lorenz Thurner, Udo Holtick, Ulrike Bacher, Bjoern Chapuy, Julia Katharina Scholz, Hristo Boyadzhiev, Thomas Melchardt, Christian Schultze‐Florey, Francis Ayuk, Andrea Kerkhoff, Evgenii Shumilov, Anna Ossami Saidy, Bertram Glass, Florian Heinrich Heidel, Amany Mokhtar Abdelhafez, Maximilian Seib, Christiane Pott
article en
18 citations

Abstract

Patients with large B-cell lymphoma (LBCL) who experience relapsed disease after CD19-directed chimeric antigen receptor (CAR) T-cell (CAR-T) therapy have a poor prognosis. Bispecific antibodies (BsAbs) induce complete remissions in ∼35% of these cases. Hypothesizing overlapping LBCL-intrinsic resistance mechanisms as well as common poor prognosis predictors to CAR-T and BsAb therapy, we conducted a multicenter retrospective analysis including 92 patients with relapsed/refractory (R/R) LBCL treated with BsAbs after CAR-T failure. Overall response rate (ORR) was 43%, with a progression-free survival (PFS) of 2.8 months. Patients receiving BsAbs during early relapse (≤3 months) achieved a significantly worse outcome (ORR, 29%; PFS, 2.2 months) compared with patients with an intermediate (4-6 months; ORR, 54%; PFS, 3.7 months) or a late relapse (>6 months; ORR, 60%; PFS, 10.5 months). The benefit of later relapse was particularly notable in patients receiving BsAbs as first salvage therapy compared with those receiving a BsAb in subsequent lines (PFS not reached vs 2.7 months; overall survival not reached vs 9.1 months, respectively). In addition to early R/R state before BsAbs, elevated lactate dehydrogenase and higher International Prognostic Index score were significant predictors of poor outcomes to BsAb in multivariate Cox regression analyses. The finding that patients with early relapse after CAR-T respond particularly poorly to BsAb highlights the necessity for alternative treatment options in this high-risk patient cohort.

Blood AdvancesVol. 9(15)
University of Bern (CH), Augsburg University (US), Universität Hamburg (DE), Paracelsus Medical University (AT), University Hospital of Bern (CH), University Hospital Augsburg (DE), Medizinische Hochschule Hannover (DE), Universitätsklinikum Erlangen (DE), Düsseldorf University Hospital (DE), MSB Medical School Berlin (DE), University Hospital Münster (DE), University Medical Center Hamburg-Eppendorf (DE), University Hospital Schleswig-Holstein (DE), Universitätsmedizin Göttingen (DE), Nephrologisches Zentrum Goettingen (DE), Essen University Hospital (DE), Cancer Research Institute of the Slovak Academy of Sciences (SK), German Marine Research Consortium (DE), Innovation Cluster (Canada) (CA), University Hospital Leipzig (DE), Jena University Hospital (DE), Unfallkrankenhaus Salzburg (AT), University Hospital Cologne (DE), University Hospital Ulm (DE), Helios Hospital Berlin-Buch (DE), West German Heart and Vascular Center Essen (DE), Klinikum Chemnitz (DE), Heinrich Heine University Düsseldorf (DE), Martin Luther University Halle-Wittenberg (DE), University of Göttingen (DE), Charité - Universitätsmedizin Berlin (DE), Saarland University (DE), University of Lübeck (DE)
Amgen, Bristol-Myers Squibb, Eli Lilly and Company, AstraZeneca, Sanofi, Gilead Sciences, Celgene, Regeneron Pharmaceuticals, Incyte, Swedish Orphan Biovitrum, MorphoSys
No poverty
Openalex Percentile: Top 1%
CAR-T cell therapy research
18.82
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.