Association of Inflammatory Markers with Disease Progression in Patients with Metastatic Melanoma Treated with Immune Checkpoint Inhibitors.

Abstract

We investigated the effect of inflammatory biomarkers (neutrophil, platelet, and lymphocyte counts) on risk of progression in patients with metastatic melanoma treated with an immune checkpoint inhibitor targeting programmed cell death protein-1 (PD-1). This retrospective cohort study included 108 patients with malignant melanoma treated with an anti-PD-1 checkpoint inhibitor from August 2014 through December 2015. The outcome was disease progression noted on imaging or clinical examination. Follow-up began on the date of initiation of anti-PD-1 therapy and ended on the date of progression, disenrollment, death of causes other than malignant melanoma, or the end of the study in February 2017. The median time from initiating therapy with an anti-PD-1 checkpoint inhibitor (nivolumab or pembrolizumab) to the end of follow-up was 118 days. After adjustment, baseline neutrophil and platelet counts were associated with progression. The hazard ratio (HR) for neutrophil counts ≥ 5501/μL vs ≤ 3900/μL was 2.3 (95% confidence interval [CI] = 1.2-4.6, p < 0.05). For platelet counts ≥ 304,000 vs ≤ 215,000/μL, the HR was 2.0 (CI = 1.0-3.9, p < 0.05). For lymphocyte counts ≥ 1716/μL vs ≤ 1120/μL, the HR was 0.5 (CI = 0.2-1.0, p = 0.05). For patients with metastatic melanoma treated with nivolumab or pembrolizumab, higher neutrophil or platelet counts, or lower lymphocyte counts, are associated with higher risk of progression. For these patients, we recommend more frequent assessment for progression and closer follow-up, especially for patients with substantial comorbidities or poor physical performance.