Neutrophil-to-lymphocyte ratio as a predictor of response and toxicity in T-cell engager therapy for solid tumors.

Abstract

e14509 Background: The neutrophil-to-lymphocyte ratio (NLR) is a well-established predictive biomarker in patients receiving immune checkpoint inhibitors (ICIs). Elevated pre-treatment NLR is linked to poorer outcomes, while lower NLR is associated with higher rates of immune-related adverse events (irAEs), likely due to neutrophil-driven immunosuppression or lymphocyte depletion impairing T-cell engagement. Bispecific T-cell engagers (TCEs), emerging immunotherapies that rely on T-cell activation, may exhibit similar patterns. We hypothesize that higher pre-treatment NLR correlates with worse survival and reduced toxicity in patients receiving TCEs. Methods: We conducted an electronic medical search at UCSF to identify patients receiving standard-of-care TCEs and investigational TCEs targeting solid tumors from 2015 to 2025. At the time of submission, a total of 29 patients with metastatic cancers receiving six different TCEs were identified. Retrospective chart review included pre-treatment complete blood counts, clinical response, and irAEs. Responses were categorized from provider notes and imaging, and irAEs were graded by the CTCAE v5. Progression-free survival (PFS), overall survival (OS), and time to severe treatment-related toxicity (grade ≥3) were calculated from the first dose of TCE with a follow-up period through January 1, 2025. NLR was calculated and stratified into high and low groups based on the median. Kaplan-Meier survival curves for OS, PFS, and time to toxicity were analyzed using a log-rank test. Results: High pre-treatment NLR was significantly associated with worse overall survival (HR: 3.87, 95% CI: 1.39–10.81) compared to low pre-treatment NLR. However, no significant difference was observed for progression-free survival (HR: 1.79, 95% CI: 0.82–3.89). No significant difference in NLR was observed between patients with and without severe irAEs (p = 0.70). Low NLR was also not linked to shorter time to severe treatment-related toxicity (HR: 1.33, 95% CI: 0.33–5.36). We aim to secure additional approvals from investigators and present further analyses with an expanded dataset at the time of presentation. Conclusions: This study highlights the potential of NLR as a predictive biomarker for overall survival in patients receiving TCEs. The lack of association between NLR and toxicity suggests TCEs may interact with immune cells through distinct mechanisms compared to ICIs. Future analyses will explore imaging responses and specific TCE toxicities such as cytokine release syndrome to better understand TCE mechanisms and refine prognostic markers.