Gustave Roussy Immune (GRIm) score validation in patients treated with Bispecific CD3 T-cell engagers in phase I clinical trials.

The Gustave Roussy Immune (GRIm)-Score, based on neutrophil-to-lymphocyte ratio, serum albumin, and lactate dehydrogenase, is a validated prognostic marker in patients receiving immune checkpoint blockers. We evaluated its prognostic value in patients treated with bispecific CD3 T cell engagers (TCEs) in phase I trials. We retrospectively analyzed prospectively collected data from 150 patients treated with TCEs alone or combined with immune checkpoint blockers across 11 phase I trials at DITEP, Gustave Roussy (June 2016-February 2025). Over-all survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier methodology and Cox regression models. Discriminatory per-formance was assessed using Harrell's C-index. Among 150 patients, 127 (85%) had solid tumors and 23 (15%) hematological malignancies; 81% were classified as low-risk GRIm-score. Low GRIm-score was associated with improved OS (HR 0.29, 95%CI 0.17-0.47, p<0.001; medi-an OS 17.6 vs 5.0 months) and PFS (HR 0.57, 95%CI 0.36-0.89, p=0.01; medi-an PFS 2.8 vs 1.6 months). In solid tumors, GRIm-score remained prognostic for OS (HR 0.41, p=0.002) but not PFS. In hematological malignancies, it strongly predicted both OS (HR 0.04, p<0.001) and PFS. Multivariable anal-yses confirmed GRIm-score as independently prognostic for OS (HR 0.29, p<0.001) and PFS (HR 0.60, p=0.035). Similar findings were observed in pa-tients receiving TCE in monotherapy. GRIm-score independently predicts outcomes in patients receiving TCEs in phase I trials and may support patient selection, particularly in hematologi-cal malignancies.