Immune-related adverse events after immune checkpoint blockade-based therapy are associated with improved survival in advanced sarcomas.

Abstract

The association between immune-related AEs (irAEs) and outcome in patients with sarcoma is not known. We retrospectively reviewed a cohort of patients with advanced sarcoma treated with immune checkpoint blockade (ICB)-based therapy. Association of irAEs with survival was assessed using a Cox regression model that incorporated irAE occurrence as a time-dependent covariate. Tumor samples with available RNA sequencing data were stratified by presence of an irAE to identify patterns of differential gene expression. A total of 131 patients were included. Forty-two (32%) had at least one irAE of any grade and 16 (12%) had at least one Grade ≥ 3 irAE. The most common irAEs were hypothyroidism (8.3%), arthralgias (5.3%), pneumonitis (4.6%), allergic reaction (3.8%), and elevated transaminases (3.8%). Median progression-free survival (PFS) and overall survival (OS) from the time of study entry were 11.4 (95% confidence interval [CI] 10.7 - 15.0) and 74.6 weeks (CI 44.9 - 89.7), respectively. On Cox analysis adjusting for clinical covariates that were significant in the univariate setting, the hazard ratio (HR) for an irAE (HR 0.662, CI 0.421 - 1.041) approached, but did not reach statistical significance for PFS (P = 0.074). Patients had a significantly lower HR for OS (HR 0.443, CI 0.246 - 0.798; P = 0.007) compared to those without or before an irAE. Gene expression profiling on baseline tumor samples found that patients who had an irAE had higher numbers of tumor-infiltrating dendritic cells, CD8+ T cells, and regulatory T cells as well as upregulation of immune and inflammatory pathways.