38 Prognostic Nutritional Index as a Predictor of Outcomes with Immune Checkpoint Inhibitors in Renal Cell Carcinoma

Résumé fourni par la source

Abstract Background Cancer cachexia has been associated with poor clinical outcomes across multiple malignancies, including renal cell carcinoma (RCC). The Prognostic Nutritional Index (PNI), a composite measure of serum albumin and lymphocyte count, has been proposed as a surrogate marker of cachexia, reflecting both nutritional and immunological status, and has been linked to adverse cancer outcomes. Herein, we evaluated the association between PNI and immune checkpoint inhibitors (ICI) outcomes in patients with metastatic RCC. Methods We included patients with biopsy proven metastatic RCC that were followed at the Sidney Kimmel Cancer Center who were treated with ICIs. PNI was calculated using the formula serum albumin (g/L) + 5 × total lymphocyte count (109/L). Patients were subdivided into a low PNI group [< 45] or a high PNI group [≥ 45] based on prior studies. We calculated the PNI of each patient on Day 0, Day 30, Day 60, and Day 90 after initiation of ICI therapy. We compared the overall survival [OS], defined as time in months from the start of ICI until death from any cause, and time-to treatment failure [TTF], defined as the start of ICI until cessation for any cause between the low and high PNI group. Both univariate and multivariate analysis were performed. Results This study included 289 patients [73% male, 27% female] with most of our study population [65%] on first line therapy while the remaining [35%] were on second line or further treatment. There was an even distribution of patients who were receiving dual ICI therapy [34%], ICI/TKI therapy [35%], and ICI monotherapy [31%]. On univariate analysis, patients with high PNI at Day 0 demonstrated significantly improved OS compared to those with low PNI, with a median OS of 47.96 months (95% CI: 36.93–57.75) versus 19.71 months (95% CI: 12.98–30.45), respectively (HR 0.56, 95% CI: 0.41–0.76; p < 0.001). A similar association was observed on Days 30, 60, and 90. At Day 0, median TTF was 7.82 months (95% CI: 4.63–11.76) in the high PNI group compared to 9.2 months (95% CI: 7.62–14.52) in the low PNI group, with no statistically significant difference between groups (HR 0.75, 95% CI: 0.56–1.02; p = 0.068). However, high PNI was associated with significantly improved TTF at Day 30 (HR 0.63, 95% CI: 0.45–0.88; p = 0.007), as well as at Days 60 and 90. On multivariable analysis, high PNI remained independently associated with improved OS at all evaluated timepoints and with improved TTF at Day 30, 60, and 90, but not at baseline (Day 0). Conclusions Pre-treatment PNI is associated with improved OS in metastatic RCC patients receiving ICI therapy, while a high PNI following D30 was predictive of improved TTF, probably reflective of dynamic tumor-host interactions and early treatment response. These findings are hypothesis generating the potential role of PNI as a biomarker of benefit to ICI therapy in metastatic RCC and warrant validation in larger prospective studies. DOD CDMRP Funding yes