Prognostic value of inflammation-based scores in patients with R/R LBCL treated with CD3×CD20 bispecific T-cell engagers

Magno G, Rejeski K, Rappa G, Stock S, Holzem A, Landwehr M, Seib M, Kutsch N, Mammadova J, Mayer S, Aumann S, Van Ham J, Ringelstein-Harlev S, Velazquez GF, Wurm-Kuczera R, Scholz JK, Greenbaum U, Raj SS, Shouval R, Müller F, Chapuy B, Schmid C, Beyar-Katz O, Vergote VK, Poeck H, Dong N, Holtick U, Ram R, Pabst T, Shumilov E, Lenz G, Iacoboni G, Barba P, Bücklein V, Subklewe M (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Blood Advances American Society of Hematology

Book Volume: 10

Pages Range: 1675-1686

Journal Issue: 5

DOI: 10.1182/bloodadvances.2025017766

Abstract

T-cell–redirecting bispecific antibodies (bsAb) offer a novel therapeutic approach for relapsed/refractory large B-cell lymphoma (R/R LBCL). However, predictive biomarkers are needed to identify patients most likely to respond. As both bsAbs and chimeric antigen receptor (CAR) T cells represent T-cell–based therapies, we hypothesized that the established CAR-HEMATOTOX (HT) and InflaMix models—reflecting the degree of systemic inflammation—could be of prognostic utility for bsAb therapy. We applied both scores to a multicenter international cohort of 174 patients with R/R LBCL treated with bsAbs across 15 sites. Patients with a high HT score (≥3, 35%) displayed inferior median progression-free (PFS; 1.4 vs 7.4 months; P < .0001) and overall survival (OS; 2.0 vs 21.7 months; P < .0001) compared with patients with a low HT score. When applying the InflaMix score, 49% of the patients were assigned to the inflammatory cluster, translating into a significantly shorter median PFS (1.9 vs 17.8 months; P < .0001) and OS (4.1 vs 21.7 months; P < .0001). In a multivariable Cox regression analysis accounting for various prognostic factors, HT and InflaMix remained independent adverse risk factors for both PFS and OS. Patients presenting with both elevated HT score and the inflammatory signature showed markedly shorter OS and PFS compared with patients deemed low-risk by either one of the scores. In the CAR-pretreated subcohort, the combination of early CAR T-cell relapse (≤3 months) and elevated inflammation led to particularly detrimental outcomes. Overall, these data highlight the prognostic utility of baseline inflammatory markers in identifying patients who may benefit from combinatorial strategies alongside bsAb.

Authors with CRIS profile

Julia Scholz Department of Medicine 5 – Haematology and Oncology Fabian Müller Department of Medicine 5 – Haematology and Oncology

Involved external institutions

Universitätsklinikum Regensburg DE Germany (DE) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven BE Belgium (BE) Rambam Health Care Campus IL Israel (IL) Ben-Gurion University of the Negev (BGU) / אוניברסיטת בן-גוריון בנגב IL Israel (IL) Memorial Sloan Kettering Cancer Center US United States (USA) (US) Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron ES Spain (ES) Klinikum der Universität München (LMU Klinikum) DE Germany (DE) Universität Augsburg DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) H. Lee Moffitt Cancer Center & Research Institute US United States (USA) (US) Universitätsklinikum Köln DE Germany (DE) Tel Aviv Sourasky Medical Center / Ichilov Hospital IL Israel (IL) Inselspital, Universitätsspital Bern CH Switzerland (CH) Universitätsklinikum Münster DE Germany (DE) Vanderbilt University US United States (USA) (US)

How to cite

APA:

Magno, G., Rejeski, K., Rappa, G., Stock, S., Holzem, A., Landwehr, M.,... Subklewe, M. (2026). Prognostic value of inflammation-based scores in patients with R/R LBCL treated with CD3×CD20 bispecific T-cell engagers. Blood Advances, 10(5), 1675-1686. https://doi.org/10.1182/bloodadvances.2025017766

MLA:

Magno, Giulia, et al. "Prognostic value of inflammation-based scores in patients with R/R LBCL treated with CD3×CD20 bispecific T-cell engagers." Blood Advances 10.5 (2026): 1675-1686.

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