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Real-world incidence and impact of pneumonitis in patients with lung cancer treated with immune checkpoint inhibitors: a multi-institutional cohort study

BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved survival and are increasingly used for non-small cell lung cancer. However, use may be limited by immune-related adverse events such as checkpoint-inhibitor pneumonitis (CIP). Literature estimates for CIP incidence are inconsistent. Real-...

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Autores principales: Tiu, Bruce C, Zubiri, Leyre, Iheke, James, Pahalyants, Vartan, Theodosakis, Nicholas, Ugwu-Dike, Pearl, Seo, Jayhyun, Tang, Kimberly, Sise, Meghan E, Sullivan, Ryan, Naidoo, Jarushka, Mooradian, Meghan J, Semenov, Yevgeniy R, Reynolds, Kerry L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204442/
https://www.ncbi.nlm.nih.gov/pubmed/35705313
http://dx.doi.org/10.1136/jitc-2022-004670
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author Tiu, Bruce C
Zubiri, Leyre
Iheke, James
Pahalyants, Vartan
Theodosakis, Nicholas
Ugwu-Dike, Pearl
Seo, Jayhyun
Tang, Kimberly
Sise, Meghan E
Sullivan, Ryan
Naidoo, Jarushka
Mooradian, Meghan J
Semenov, Yevgeniy R
Reynolds, Kerry L
author_facet Tiu, Bruce C
Zubiri, Leyre
Iheke, James
Pahalyants, Vartan
Theodosakis, Nicholas
Ugwu-Dike, Pearl
Seo, Jayhyun
Tang, Kimberly
Sise, Meghan E
Sullivan, Ryan
Naidoo, Jarushka
Mooradian, Meghan J
Semenov, Yevgeniy R
Reynolds, Kerry L
author_sort Tiu, Bruce C
collection PubMed
description BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved survival and are increasingly used for non-small cell lung cancer. However, use may be limited by immune-related adverse events such as checkpoint-inhibitor pneumonitis (CIP). Literature estimates for CIP incidence are inconsistent. Real-world adherence to guidelines, clinical course, and healthcare utilization in the treatment of CIP has not been described in large cohorts. METHODS: A combined claims and electronic health record database (TriNetX) was used to identify 13,113 patients with lung cancer treated with programmed cell death receptor/ligand 1 (PD-1/PD-L1) inhibitors, and a propensity score-matched control cohort treated with chemotherapy or targeted therapies. The attributable risk of CIP was calculated in the first 12 months after therapy by comparing the incidence of diagnosis codes for pneumonitis/pneumonia between cohorts. Cases of CIP, identified by the most specific code for drug-induced respiratory conditions, were further analyzed for medication usage, rates of diagnostic bronchoscopy, ICI discontinuation rates, and usage of hospital services compared with patients receiving PD-1/PD-L1 inhibitors who did not develop CIP. RESULTS: The attributable risk of pneumonitis to PD-1/PD-L1 inhibitors was 2.49% (95% CI, 1.50% to 3.47%). Median time to onset in the CIP subcohort was 3.9 months (IQR, 2.1–7.3 months). Steroid and antibiotic use increased dramatically after a pneumonitis diagnosis, and 70.2% of patients permanently discontinued ICI therapy. Compared with controls, patients with CIP had more than a threefold increased risk of needing critical care (relative risk 3.59, 95% CI, 2.31 to 5.57) and an increased risk of mortality (HR 2.34, 95% CI, 1.47 to 3.71). CONCLUSIONS: In a large claims-based analysis, PD-1/PD-L1 inhibitors increase the risk of pneumonitis in patients with lung cancer by 2.49%. Cases of CIP are associated with high healthcare utilization, discontinuation of ICIs, and mortality.
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spelling pubmed-92044422022-06-29 Real-world incidence and impact of pneumonitis in patients with lung cancer treated with immune checkpoint inhibitors: a multi-institutional cohort study Tiu, Bruce C Zubiri, Leyre Iheke, James Pahalyants, Vartan Theodosakis, Nicholas Ugwu-Dike, Pearl Seo, Jayhyun Tang, Kimberly Sise, Meghan E Sullivan, Ryan Naidoo, Jarushka Mooradian, Meghan J Semenov, Yevgeniy R Reynolds, Kerry L J Immunother Cancer Clinical/Translational Cancer Immunotherapy BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved survival and are increasingly used for non-small cell lung cancer. However, use may be limited by immune-related adverse events such as checkpoint-inhibitor pneumonitis (CIP). Literature estimates for CIP incidence are inconsistent. Real-world adherence to guidelines, clinical course, and healthcare utilization in the treatment of CIP has not been described in large cohorts. METHODS: A combined claims and electronic health record database (TriNetX) was used to identify 13,113 patients with lung cancer treated with programmed cell death receptor/ligand 1 (PD-1/PD-L1) inhibitors, and a propensity score-matched control cohort treated with chemotherapy or targeted therapies. The attributable risk of CIP was calculated in the first 12 months after therapy by comparing the incidence of diagnosis codes for pneumonitis/pneumonia between cohorts. Cases of CIP, identified by the most specific code for drug-induced respiratory conditions, were further analyzed for medication usage, rates of diagnostic bronchoscopy, ICI discontinuation rates, and usage of hospital services compared with patients receiving PD-1/PD-L1 inhibitors who did not develop CIP. RESULTS: The attributable risk of pneumonitis to PD-1/PD-L1 inhibitors was 2.49% (95% CI, 1.50% to 3.47%). Median time to onset in the CIP subcohort was 3.9 months (IQR, 2.1–7.3 months). Steroid and antibiotic use increased dramatically after a pneumonitis diagnosis, and 70.2% of patients permanently discontinued ICI therapy. Compared with controls, patients with CIP had more than a threefold increased risk of needing critical care (relative risk 3.59, 95% CI, 2.31 to 5.57) and an increased risk of mortality (HR 2.34, 95% CI, 1.47 to 3.71). CONCLUSIONS: In a large claims-based analysis, PD-1/PD-L1 inhibitors increase the risk of pneumonitis in patients with lung cancer by 2.49%. Cases of CIP are associated with high healthcare utilization, discontinuation of ICIs, and mortality. BMJ Publishing Group 2022-06-15 /pmc/articles/PMC9204442/ /pubmed/35705313 http://dx.doi.org/10.1136/jitc-2022-004670 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Clinical/Translational Cancer Immunotherapy
Tiu, Bruce C
Zubiri, Leyre
Iheke, James
Pahalyants, Vartan
Theodosakis, Nicholas
Ugwu-Dike, Pearl
Seo, Jayhyun
Tang, Kimberly
Sise, Meghan E
Sullivan, Ryan
Naidoo, Jarushka
Mooradian, Meghan J
Semenov, Yevgeniy R
Reynolds, Kerry L
Real-world incidence and impact of pneumonitis in patients with lung cancer treated with immune checkpoint inhibitors: a multi-institutional cohort study
title Real-world incidence and impact of pneumonitis in patients with lung cancer treated with immune checkpoint inhibitors: a multi-institutional cohort study
title_full Real-world incidence and impact of pneumonitis in patients with lung cancer treated with immune checkpoint inhibitors: a multi-institutional cohort study
title_fullStr Real-world incidence and impact of pneumonitis in patients with lung cancer treated with immune checkpoint inhibitors: a multi-institutional cohort study
title_full_unstemmed Real-world incidence and impact of pneumonitis in patients with lung cancer treated with immune checkpoint inhibitors: a multi-institutional cohort study
title_short Real-world incidence and impact of pneumonitis in patients with lung cancer treated with immune checkpoint inhibitors: a multi-institutional cohort study
title_sort real-world incidence and impact of pneumonitis in patients with lung cancer treated with immune checkpoint inhibitors: a multi-institutional cohort study
topic Clinical/Translational Cancer Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204442/
https://www.ncbi.nlm.nih.gov/pubmed/35705313
http://dx.doi.org/10.1136/jitc-2022-004670
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