Tumor location as a risk factor for severe immune-related adverse events

Immune-related adverse events (irAEs) can cause severe morbidity and mortality, and they impair treatment with immune checkpoint inhibitors (ICI). Risk factors for irAEs are not well understood.We observed cases of patients having tumor deposits in their liver and lung during a workup of irAEs, whic...

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Main Authors: Mike Wang, Michael Dougan, Daniel Leonard, Leyre Zubiri, Ryan J Sullivan, Kerry L Reynolds, Donald P Lawrence, Kamil Slowikowski, Alexandra-Chloe Villani, Steven M Blum, Ben Ouyang, Kelley A Grealish, Nora K Hathaway, Gabriel Molina, Nishi Shah, Mari Mino Kendusen
Format: Article
Language:English
Published: BMJ Publishing Group 2025-05-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/13/5/e011312.full
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author Mike Wang
Michael Dougan
Daniel Leonard
Leyre Zubiri
Ryan J Sullivan
Kerry L Reynolds
Donald P Lawrence
Kamil Slowikowski
Alexandra-Chloe Villani
Steven M Blum
Ben Ouyang
Kelley A Grealish
Nora K Hathaway
Gabriel Molina
Nishi Shah
Mari Mino Kendusen
author_facet Mike Wang
Michael Dougan
Daniel Leonard
Leyre Zubiri
Ryan J Sullivan
Kerry L Reynolds
Donald P Lawrence
Kamil Slowikowski
Alexandra-Chloe Villani
Steven M Blum
Ben Ouyang
Kelley A Grealish
Nora K Hathaway
Gabriel Molina
Nishi Shah
Mari Mino Kendusen
author_sort Mike Wang
collection DOAJ
description Immune-related adverse events (irAEs) can cause severe morbidity and mortality, and they impair treatment with immune checkpoint inhibitors (ICI). Risk factors for irAEs are not well understood.We observed cases of patients having tumor deposits in their liver and lung during a workup of irAEs, which led us to hypothesize that the presence of tumor in an organ would increase the odds of developing severe irAEs in that organ. We then performed a retrospective cohort study that included patients who received an ICI for the treatment of cancer and were hospitalized between February 2011 and November 2021 at the Massachusetts General Hospital.We reviewed 384 patients hospitalized with concern for any irAE. A clinical diagnosis of ICI-related hepatitis occurred in 18% of patients with liver tumor deposits versus 8% of those without (OR 2.23, 95% CI (1.10 to 4.43), p=0.02). ICI-related pneumonitis occurred in 10% of patients with lung tumor deposits versus 4.4% of those without (OR 2.45, 95% CI (1.06 to 6.36), p=0.047). A combined analysis for liver and lung lesions demonstrated that the presence of tumor deposits in an organ increased the odds of having an irAE in that organ by over twofold (OR 2.31, 95% CI (1.34 to 3.99), p=0.002).Our results suggest that the presence of tumor deposits may represent a novel risk factor for severe irAEs in that organ.
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spelling doaj-art-6eb03374fedb422488c2a4fb1bcc0a8a2025-08-20T01:51:01ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-05-0113510.1136/jitc-2024-011312Tumor location as a risk factor for severe immune-related adverse eventsMike Wang0Michael Dougan1Daniel Leonard2Leyre Zubiri3Ryan J Sullivan4Kerry L Reynolds5Donald P Lawrence6Kamil Slowikowski7Alexandra-Chloe Villani8Steven M Blum9Ben Ouyang10Kelley A Grealish11Nora K Hathaway12Gabriel Molina13Nishi Shah14Mari Mino Kendusen153 Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA2 Harvard Medical School, Boston, Massachusetts, USA2 Harvard Medical School, Boston, Massachusetts, USA1 Medical Oncology, Mass General Cancer Center, Boston, Massachusetts, USA1 Medical Oncology, Mass General Cancer Center, Boston, Massachusetts, USA1 Medical Oncology, Mass General Cancer Center, Boston, Massachusetts, USA2 Harvard Medical School, Boston, Massachusetts, USA2 Harvard Medical School, Boston, Massachusetts, USA5 Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA1 Medical Oncology, Mass General Cancer Center, Boston, Massachusetts, USA1 Medical Oncology, Mass General Cancer Center, Boston, Massachusetts, USA1 Medical Oncology, Mass General Cancer Center, Boston, Massachusetts, USA1 Medical Oncology, Mass General Cancer Center, Boston, Massachusetts, USA2 Harvard Medical School, Boston, Massachusetts, USA2 Harvard Medical School, Boston, Massachusetts, USA2 Harvard Medical School, Boston, Massachusetts, USAImmune-related adverse events (irAEs) can cause severe morbidity and mortality, and they impair treatment with immune checkpoint inhibitors (ICI). Risk factors for irAEs are not well understood.We observed cases of patients having tumor deposits in their liver and lung during a workup of irAEs, which led us to hypothesize that the presence of tumor in an organ would increase the odds of developing severe irAEs in that organ. We then performed a retrospective cohort study that included patients who received an ICI for the treatment of cancer and were hospitalized between February 2011 and November 2021 at the Massachusetts General Hospital.We reviewed 384 patients hospitalized with concern for any irAE. A clinical diagnosis of ICI-related hepatitis occurred in 18% of patients with liver tumor deposits versus 8% of those without (OR 2.23, 95% CI (1.10 to 4.43), p=0.02). ICI-related pneumonitis occurred in 10% of patients with lung tumor deposits versus 4.4% of those without (OR 2.45, 95% CI (1.06 to 6.36), p=0.047). A combined analysis for liver and lung lesions demonstrated that the presence of tumor deposits in an organ increased the odds of having an irAE in that organ by over twofold (OR 2.31, 95% CI (1.34 to 3.99), p=0.002).Our results suggest that the presence of tumor deposits may represent a novel risk factor for severe irAEs in that organ.https://jitc.bmj.com/content/13/5/e011312.full
spellingShingle Mike Wang
Michael Dougan
Daniel Leonard
Leyre Zubiri
Ryan J Sullivan
Kerry L Reynolds
Donald P Lawrence
Kamil Slowikowski
Alexandra-Chloe Villani
Steven M Blum
Ben Ouyang
Kelley A Grealish
Nora K Hathaway
Gabriel Molina
Nishi Shah
Mari Mino Kendusen
Tumor location as a risk factor for severe immune-related adverse events
Journal for ImmunoTherapy of Cancer
title Tumor location as a risk factor for severe immune-related adverse events
title_full Tumor location as a risk factor for severe immune-related adverse events
title_fullStr Tumor location as a risk factor for severe immune-related adverse events
title_full_unstemmed Tumor location as a risk factor for severe immune-related adverse events
title_short Tumor location as a risk factor for severe immune-related adverse events
title_sort tumor location as a risk factor for severe immune related adverse events
url https://jitc.bmj.com/content/13/5/e011312.full
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