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

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

Authors:	Rosenbaum, E.; Seier, K.; Bradic, M.; Kelly, C.; Movva, S.; Nacev, B. A.; Gounder, M. M.; Keohan, M. L.; Avutu, V.; Chi, P.; Thornton, K. A.; Chan, J. E.; Dickson, M. A.; Donoghue, M. T. A.; Tap, W. D.; Qin, L. X.; D'Angelo, S. P.
Article Title:	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 (irAE) 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 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 with 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.Significance: irAE after ICB therapy was associated with an improved OS; it also approached statistical significance for improved PFS. Patients who had an irAE were more likely to have an inflamed tumor microenvironment at baseline.
Keywords:	tumor; regression; open-label; nivolumab; cancer
Journal Title:	Cancer Research Communications
Volume:	3
Issue:	10
ISSN:	2767-9764
Publisher:	American Association for Cancer Research
Date Published:	2023-10-01
Start Page:	2118
End Page:	2125
Language:	English
ACCESSION:	WOS:001104278200005
DOI:	10.1158/2767-9764.Crc-22-0140
PROVIDER:	wos
PMCID:	PMC10583739
PUBMED:	37787759
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Evan Rosenbaum -- Source: Wos