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.