Prognostic value of inflammation-based scores in patients with R/R LBCL treated with CD3×CD20 bispecific T-cell engagers
Year: 2025
Type: article
Study design: Observational Study
Abstract: 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.
Source: Blood Advances
Authors: Giulia Magno, Kai Rejeski, Giulia Rappa, Sophia Stock, Alessandra Holzem, Maria Landwehr, Maximilian Seib, Nadine Kutsch, Jamila Mammadova, Stephanie Mayer, Shlomzion Aumann, Jonas Van Ham, Shimrit Ringelstein-Harlev, Giuliano Filippini Velazquez, Rebecca Wurm-Kuczera, Julia Katharina Scholz, Uri Greenbaum, Sandeep S. Raj, Roni Shouval, Fabian Müller, Björn Chapuy, Christoph Schmid, Ofrat Beyar-Katz, Vibeke K. J. Vergote, Hendrik Poeck, Ning Dong, Udo Holtick, Ron Ram, Thomas Pabst, Evgenii Shumilov, Georg Lenz, Gloria Iacoboni, Pere Barba, Veit Bücklein, Marion Subklewe
Institutions: German Cancer Research Center, LMU Klinikum, Ludwig-Maximilians-Universität München, Memorial Sloan Kettering Cancer Center, Vall d'Hebron Hospital Universitari, University Hospital Münster, University of Cologne, University of Münster, University Hospital Cologne, Vanderbilt University Medical Center, University Hospital Regensburg, Hebrew University of Jerusalem, Hadassah Medical Center, Universitair Ziekenhuis Leuven, Rambam Health Care Campus, University Hospital Augsburg, University of Augsburg, Stiftung Charité, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Universitätsklinikum Erlangen, Freie Universität Berlin, Soroka Medical Center, Ben-Gurion University of the Negev, Weill Cornell Medicine, Moffitt Cancer Center, Tel Aviv Sourasky Medical Center, University Hospital of Bern, Vall d'Hebron Institute of Oncology
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
Funders: 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, National Cancer Institute
OpenAlex ID: W4415442918