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Immune-related Adverse Events after Immune Checkpoint Blockade–based Therapy Are Associated with Improved Survival in Advanced Sarcomas

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 regress...

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Autores principales: Rosenbaum, Evan, Seier, Kenneth, Bradic, Martina, Kelly, Ciara, Movva, Sujana, Nacev, Benjamin A., Gounder, Mrinal M., Keohan, Mary L., Avutu, Viswatej, Chi, Ping, Thornton, Katherine A., Chan, Jason E., Dickson, Mark A., Donoghue, Mark T.A., Tap, William D., Qin, Li-Xuan, D'Angelo, Sandra P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for Cancer Research 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10583739/
https://www.ncbi.nlm.nih.gov/pubmed/37787759
http://dx.doi.org/10.1158/2767-9764.CRC-22-0140
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author Rosenbaum, Evan
Seier, Kenneth
Bradic, Martina
Kelly, Ciara
Movva, Sujana
Nacev, Benjamin A.
Gounder, Mrinal M.
Keohan, Mary L.
Avutu, Viswatej
Chi, Ping
Thornton, Katherine A.
Chan, Jason E.
Dickson, Mark A.
Donoghue, Mark T.A.
Tap, William D.
Qin, Li-Xuan
D'Angelo, Sandra P.
author_facet Rosenbaum, Evan
Seier, Kenneth
Bradic, Martina
Kelly, Ciara
Movva, Sujana
Nacev, Benjamin A.
Gounder, Mrinal M.
Keohan, Mary L.
Avutu, Viswatej
Chi, Ping
Thornton, Katherine A.
Chan, Jason E.
Dickson, Mark A.
Donoghue, Mark T.A.
Tap, William D.
Qin, Li-Xuan
D'Angelo, Sandra P.
author_sort Rosenbaum, Evan
collection PubMed
description 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.
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spelling pubmed-105837392023-10-19 Immune-related Adverse Events after Immune Checkpoint Blockade–based Therapy Are Associated with Improved Survival in Advanced Sarcomas Rosenbaum, Evan Seier, Kenneth Bradic, Martina Kelly, Ciara Movva, Sujana Nacev, Benjamin A. Gounder, Mrinal M. Keohan, Mary L. Avutu, Viswatej Chi, Ping Thornton, Katherine A. Chan, Jason E. Dickson, Mark A. Donoghue, Mark T.A. Tap, William D. Qin, Li-Xuan D'Angelo, Sandra P. Cancer Res Commun Research Article 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. American Association for Cancer Research 2023-10-18 /pmc/articles/PMC10583739/ /pubmed/37787759 http://dx.doi.org/10.1158/2767-9764.CRC-22-0140 Text en © 2023 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by/4.0/This open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.
spellingShingle Research Article
Rosenbaum, Evan
Seier, Kenneth
Bradic, Martina
Kelly, Ciara
Movva, Sujana
Nacev, Benjamin A.
Gounder, Mrinal M.
Keohan, Mary L.
Avutu, Viswatej
Chi, Ping
Thornton, Katherine A.
Chan, Jason E.
Dickson, Mark A.
Donoghue, Mark T.A.
Tap, William D.
Qin, Li-Xuan
D'Angelo, Sandra P.
Immune-related Adverse Events after Immune Checkpoint Blockade–based Therapy Are Associated with Improved Survival in Advanced Sarcomas
title Immune-related Adverse Events after Immune Checkpoint Blockade–based Therapy Are Associated with Improved Survival in Advanced Sarcomas
title_full Immune-related Adverse Events after Immune Checkpoint Blockade–based Therapy Are Associated with Improved Survival in Advanced Sarcomas
title_fullStr Immune-related Adverse Events after Immune Checkpoint Blockade–based Therapy Are Associated with Improved Survival in Advanced Sarcomas
title_full_unstemmed Immune-related Adverse Events after Immune Checkpoint Blockade–based Therapy Are Associated with Improved Survival in Advanced Sarcomas
title_short Immune-related Adverse Events after Immune Checkpoint Blockade–based Therapy Are Associated with Improved Survival in Advanced Sarcomas
title_sort immune-related adverse events after immune checkpoint blockade–based therapy are associated with improved survival in advanced sarcomas
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10583739/
https://www.ncbi.nlm.nih.gov/pubmed/37787759
http://dx.doi.org/10.1158/2767-9764.CRC-22-0140
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