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

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

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-intri...

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Main Authors: Evgenii Shumilov, Julia Katharina Scholz, Maximilian Seib, Paolo Mazzeo, Rebecca Wurm-Kuczera, Vladan Vucinic, Udo Holtick, Hristo Boyadzhiev, Thomas Melchardt, Alexander Hölscher, Christian Schultze-Florey, Atef Abdelhafez, Giuliano Filippini Velazquez, Anna Ossami Saidy, Vadim Lesan, Ulf Schnetzke, Andrea Kerkhoff, Ulrike Bacher, Susanne Ghandili, Enver Aydilek, Niklas Gebauer, Thomas Weber, Gerald Wulf, Bertram Glass, Lorenz Thurner, Florian H. Heidel, Christoph Schmid, Andreas Viardot, Mathias Hänel, Sascha Dietrich, Thomas Pabst, Francis Ayuk, Bastian von Tresckow, Björn Chapuy, Christiane Pott, Fabian Müller, Georg Lenz
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Blood Advances
Online Access:http://www.sciencedirect.com/science/article/pii/S2473952925002289
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Summary: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.
ISSN:2473-9529

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