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

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.

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Publication Details

Journal
Blood Advances
Published
2025-10-22
DOI
https://doi.org/10.1182/bloodadvances.2025017766
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Alessandra Holzem, Christoph Schmid, Sophia Stock, Jonas Van Ham et al.
Blood Advances
CAR-T cell therapy research
article

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

Alessandra Holzem, Christoph Schmid, Sophia Stock, Jonas Van Ham, Udo Holtick, Giuliano Filippini Velázquez, Shlomzion Aumann, Roni Shouval, Ofrat Beyar‐Katz, Ning Dong, Fabian Müller, Georg Lenz, Gloria Iacoboni, Veit Bücklein, Hendrik Poeck, Thomas Pabst, Nadine Kutsch, Rebecca Wurm‐Kuczera, Ron Ram, Jamila Mammadova, Pere Barba, Sandeep S. Raj, Stephanie Mayer, Uri Greenbaum, Julia Katharina Scholz, Shimrit Ringelstein‐Harlev, Evgenii Shumilov, Giulia Magno, Vibeke Vergote, Giulia Rappa, Maria Landwehr, Maximilian Seib
article en

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.

Blood AdvancesVol. 10(5)
Ben-Gurion University of the Negev (IL), Memorial Sloan Kettering Cancer Center (US), German Cancer Research Center (DE), University of Cologne (DE), Hebrew University of Jerusalem (IL), Cornell University (US), Heidelberg University (DE), Tel Aviv Sourasky Medical Center (IL), Hadassah Medical Center (IL), Universitair Ziekenhuis Leuven (BE), Soroka Medical Center (IL), University Hospital of Bern (CH), Rambam Health Care Campus (IL), University Hospital Augsburg (DE), University Hospital Heidelberg (DE), LMU Klinikum (DE), Moffitt Cancer Center (US), University Hospital Regensburg (DE), Humboldt-Universität zu Berlin (DE), Universitätsklinikum Erlangen (DE), Düsseldorf University Hospital (DE), Integrated Oncology (United States) (US), German Cancer Society (DE), University Hospital Münster (DE), Vall d'Hebron Hospital Universitari (ES), University Hospital Cologne (DE), Vall d'Hebron Institute of Oncology (ES), Heinrich Heine University Düsseldorf (DE), Charité - Universitätsmedizin Berlin (DE), Ludwig-Maximilians-Universität München (DE), Vanderbilt University Medical Center (US), KU Leuven (BE)
Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, Sanofi, Gilead Sciences, Celgene, F. Hoffmann-La Roche, Les Laboratories Pierre Fabre, Agios Pharmaceuticals, BeiGene, Incyte, Deutsche Forschungsgemeinschaft, Swedish Orphan Biovitrum, MorphoSys
Openalex Percentile: Top 60%
CAR-T cell therapy research
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