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

Shumilov E, Scholz J, Seib M, Mazzeo P, Wurm-Kuczera R, Vucinic V, Holtick U, Boyadzhiev H, Melchardt T, Hölscher A, Schultze-Florey C, Abdelhafez A, Filippini Velazquez G, Ossami Saidy A, Lesan V, Schnetzke U, Kerkhoff A, Bacher U, Ghandili S, Aydilek E, Gebauer N, Weber T, Wulf G, Glass B, Thurner L, Heidel F, Schmid C, Viardot A, Hänel M, Dietrich S, Pabst T, Ayuk F, von Tresckow B, Chapuy B, Pott C, Müller F, Lenz G (2025)

Publication Language: English

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 9

Pages Range: 3955-3966

Journal Issue: 15

DOI: 10.1182/bloodadvances.2024015719

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.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Göttingen Germany (DE) Inselspital, Universitätsspital Bern Switzerland (CH) Universitätsklinikum Leipzig Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Universitätsklinikum Münster Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Universitätsklinikum Düsseldorf Germany (DE) Klinikum Chemnitz Germany (DE) Universitätsklinikum Ulm Germany (DE) Universitätsklinikum Augsburg Germany (DE) Universitätsklinikum des Saarlandes (UKS) Germany (DE) Universitätsklinikum Halle (Saale) Germany (DE) Universitätsklinikum Jena Germany (DE) Universitätsklinikum Essen Germany (DE) Universitätsklinikum Köln Germany (DE) Helios Klinikum Berlin-Buch / Helios Hospital Berlin-Buch Germany (DE) Paracelsus Medizinische Privatuniversität Austria (AT)

How to cite

APA:

Shumilov, E., Scholz, J., Seib, M., Mazzeo, P., Wurm-Kuczera, R., Vucinic, V.,... Lenz, G. (2025). Outcomes of bispecific antibody therapy after CAR T-cell failure in relapsed/refractory large B-cell lymphoma. Blood Advances, 9(15), 3955-3966. https://doi.org/10.1182/bloodadvances.2024015719

MLA:

Shumilov, Evgenii, et al. "Outcomes of bispecific antibody therapy after CAR T-cell failure in relapsed/refractory large B-cell lymphoma." Blood Advances 9.15 (2025): 3955-3966.

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