Development and external validation of a prognostic score associated with poor outcomes in patients receiving immune checkpoint blockade-containing therapies enrolled in early-phase clinical trials.

BACKGROUND

Immune checkpoint blockade (ICB) has transformed cancer treatment, yet many patients experience poor outcomes. Identifying patients at high risk of poor outcomes under ICB-containing therapies remains a major clinical challenge.

OBJECTIVES

To identify baseline factors associated with poor outcomes under ICB-containing therapies and develop a prognostic score for early-phase clinical trials.

METHODS

We analyzed a discovery cohort of patients with advanced solid tumors receiving ICB-containing therapies in early-phase clinical trials at Gustave Roussy Cancer Center (DITEP), derived from the prospective PREMIS study (NCT03984318). Baseline clinical and biological variables were evaluated in relation to survival outcomes, and a multivariable Cox model was used to identify independent prognostic factors. A simple five-factor prognostic score was subsequently developed using biologically relevant baseline variables and externally validated in an independent cohort from Institut Curie.

RESULTS

Among 227 patients, a prognostic score incorporating liver metastases, elevated neutrophil count, elevated CRP, elevated LDH, and low lymphocyte count was developed (one point per factor, range 0-5). ECOG performance status, absolute neutrophil count, and absolute lymphocyte count remained independently associated with overall survival after adjustment. Patients with a score ≥ 3 had significantly shorter overall survival than those with a score of 0 (HR 4.10, 95% CI 1.71-10.00; p = 0.002), confirmed in external validation (HR 2.22, 95% CI 1.21-4.08; p = 0.006). The score discriminated overall survival better than RMH and LIPI, with similar performance to GRIm-Score and MDA-ICI.

CONCLUSION

We developed and externally validated a simple prognostic score identifying patients at high risk of poor outcomes during ICB-containing therapies in early-phase trials. This tool may improve baseline risk stratification but should not be used as an exclusion criterion for enrollment.