Peripheral blood cell counts as biomarkers of clinical benefit in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC) receiving immune checkpoint inhibitor (ICI) combination (combo) therapies.

Abstract

446 Background: Numerous combos of ICIs and Tyrosine Kinase Inhibitors (TKIs) have received approval for the management of mccRCC. Specific peripheral blood cell counts reflect inflammation and impact anti-tumor immunity, and here we investigated their role as biomarkers of clinical benefit to ICI combos in RCC. Methods: We performed a retrospective study of 179 mccRCC patients treated with ICI combos ≥ 4 weeks (2013-2023), where we examined baseline and 6-week post-treatment Neutrophil to Lymphocyte ratio (NLR), Red cell Distribution Width (RDW), and eosinophil values. We categorized these values as High (H) or Low (L) based on baseline medians. Our analysis included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to next treatment (TNT). Kaplan-Meier methods and the log-rank test were used to evaluate time from start of ICI combos to the event of interest. Results: Our analysis included 111 eligible ICI-naïve mccRCC patients median age 63, 76% male. IMDC risk scores categorized 22% as favorable, 53% intermediate, and 25% poor risk. Treatment included 50 (45%) patients on ICI+ICI combos with a median therapy duration of 6.3 months, and 61 (55%) on ICI+TKI with a median duration of 8.8 months. In the ICI+ICI group, median OS was 28.2 months (95% CI 20.7-38.4), PFS 5.5 months (95% CI 3.7-7.8), and TNT 12.7 months (95% CI 7.4-20.4). In the ICI+TKI group, median OS was 21.7 months (95% CI 17.1-25.4), PFS 7.4 months (95% CI 5.6-11.1), and TNT 12.5 months (95% CI 9.7-16.4). The ORR was 38% in the ICI+ICI group, and 56% in the ICI+TKI group (p=0.062). No differences were seen with NLR. In the ICI+ICI group, higher baseline RDW levels were correlated with a shorter TNT, while higher eosinophil levels at week 6 were correlated with longer PFS and TNT (significant results highlighted in the table below). Conclusions: Eosinophil levels and RDW are potentially readily available biomarkers in the clinic for predicting and monitoring ICI combo treatment outcomes in mccRCC patients. Validation of these results in larger cohorts is warranted. [Table: see text]