Relationship of lymphocyte and eosinophil counts and immune-related adverse events in recipients of programmed death-1 (PD-1) inhibitor therapy: A single-center retrospective analysis.

Abstract

e14586 Background: Inhibition of the PD-1 checkpoint can cause immune activation in non-target tissues, resulting in immune-related adverse events (irAE) in up to 50% of patients. Biomarkers that are associated with irAEs in patients treated with PD-1 inhibitors may have implications for patient selection and clinical management. Methods: We performed an IRB-approved retrospective chart review of adult solid tumor patients treated with nivolumab or pembrolizumab at a single institution from January 2015 until November 2016. Patients were excluded if concurrently receiving investigational therapies, or on unreported clinical trials. Data were collected on treatment history, leukocyte counts, and irAE, defined as adverse events with a potential immunologic basis with grading performed using CTCAE v.4.0. Results: 172 patients were included (lung n = 54; melanoma n = 61; kidney n = 25; esophageal n = 12; bladder n = 8; other tumors n = 12) with median age 67. 18% were treated with concurrent ipilimumab. 31% experienced an adverse event of any grade with a mean time to develop an irAE of 3.5 months. Of those with an irAE, 85% required treatment, 68% were grade ≥ 2, 32% were grade 3 or 4 and 35% required therapy discontinuation due to the irAE. In univariate analysis, a higher ALC at both the start of therapy and at 1 month was associated with increased risk of an irAE of grade ≥ 2 (p < 0.05). A higher absolute lymphocyte count (ALC) or higher absolute eosinophil count (AEC) at 1 month into therapy was associated with increased risk of all irAE (p < 0.05) as well as irAE requiring treatment (p < 0.05). In addition, in a multivariate regression analysis including age, race, tumor type, prior chemotherapy, prior radiation, and concurrent ipilimumab therapy, an ALC > 2000 at the start of therapy was a significant predictor of irAE of grade ≥ 2 (p < 0.05 and OR 2.0), as was an ALC > 2000 at 1 month into therapy (p < 0.05 and OR 1.86). Conclusions: These results suggest that high lymphocyte and eosinophil counts early in the course of anti-PD1 therapy may be associated with a higher risk for clinically significant irAE.