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Cited by 1,215Cancer Immunotherapy and BiomarkersInterstitial Lung Diseases and Idiopathic Pulmonary FibrosisImmunotoxicology and immune responses

Pneumonitis in Patients Treated With Anti–Programmed Death-1/Programmed Death Ligand 1 Therapy

Open access
Naidoo, Jarushka, Wang, Xuan, Woo, Kaitlin M., Iyriboz, Tunc, Halpenny, Darragh, Cunningham, Jane, Chaft, Jamie E., Segal, Neil H. +21 more·2017·Journal of Clinical Oncology
DOI 10.1200/jco.2016.68.2005PMC PMC5559901
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Abstract

Purpose: Pneumonitis is an uncommon but potentially fatal toxicity of anti–programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) monoclonal antibodies (mAbs). Clinical, radiologic, and pathologic features are poorly described. Methods: Patients who received anti–PD-1/PD-L1 monotherapy or in combination with anti–cytotoxic T-cell lymphocyte associated antigen-4 mAb were identified at two institutions (Memorial Sloan Kettering Cancer Center: advanced solid cancers, 2009 to 2014, and Melanoma Institute of Australia: melanomas only, 2013 to 2015). Pneumonitis was diagnosed by the treating investigator; cases with confirmed malignant lung infiltration or infection were excluded. Clinical, radiologic, and pathologic features of pneumonitis were collected. Associations among pneumonitis incidence, therapy received, and underlying malignancy were examined with Fisher’s exact test as were associations between pneumonitis features and outcomes. Results: Of 915 patients who received anti–PD-1/PD-L1 mAbs, pneumonitis developed in 43 (5%; 95% CI, 3% to 6%; Memorial Sloan Kettering Cancer Center, 27 of 578 [5%]; Melanoma Institute of Australia, 16 of 337 [5%]). Time to onset of pneumonitis ranged from 9 days to 19.2 months. The incidence of pneumonitis was higher with combination immunotherapy versus monotherapy (19 of 199 [10%] v 24 of 716 [3%]; P < .01). Incidence was similar in patients with melanoma and non–small-cell lung cancer (overall, 26 of 532 [5%] v nine of 209 [4%]; monotherapy, 15 of 417 v five of 152 [ P = 1.0]; combination, 11 of 115 v four of 57 [ P = .78]). Seventy-two percent (31 of 43) of cases were grade 1 to 2, and 86% (37 of 43) improved/resolved with drug holding/immunosuppression. Five patients worsened clinically and died during the course of pneumonitis treatment; proximal cause of death was pneumonitis (n = 1), infection related to immunosuppression (n = 3), or progressive cancer (n = 1). Radiologic and pathologic features of pneumonitis were diverse. Conclusion: Pneumonitis associated with anti–PD-1/PD-L1 mAbs is a toxicity of variable onset and clinical, radiologic, and pathologic appearances. It is more common when anti–PD-1/PD-L1 mAbs are combined with anti–cytotoxic T-cell lymphocyte associated antigen-4 mAb. Most events are low grade and improve/resolve with drug holding/immunosuppression. Rarely, pneumonitis worsens despite immunosuppression, and may result in infection and/or death.

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Crossref · 10.1200/jco.2016.68.2005

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  • Patients with pre-existing anti-thyroid antibodies have a much higher risk of thyroid dysfunction; three studies reported 20-50% versus 1-2.5% in antibody-negative patients.

    “three studies showed that patients with antithyroglobulin or anti-thyroid peroxidase antibodies had a much higher risk of thyroid dysfunction compared with patients negative for these antibodies (20-50% vs. 1-2.5%).41–43”

    From Endocrine toxicities of immune checkpoint inhibitors (2021) · cites this paper as [41]

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Authors
Naidoo, J., Wang, X., Woo, K. M., Iyriboz, T., Halpenny, D., Cunningham, J., Chaft, J. E., Segal, N. H., Callahan, M. K., Lesokhin, A. M., Rosenberg, J., Voss, M. H., Rudin, C. M., Rizvi, H., Hou, X., Rodriguez, K., Albano, M., Gordon, R.-A., Leduc, C., Rekhtman, N., Harris, B., Menzies, A. M., Guminski, A. D., Carlino, M. S., Kong, B. Y., Wolchok, J. D., Postow, M. A., Long, G. V., & Hellmann, M. D.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • Jarushka Naidoo, Kaitlin M. Woo, Tunc Iyriboz, Darragh Halpenny, Jane Cunningham, Jamie E. Chaft, Neil H. Segal, Margaret K. Callahan, Alexander M. Lesokhin, Jonathan Rosenberg, Martin H. Voss, Charles M. Rudin, Hira Rizvi, Xue Hou, Katherine Rodriguez, Melanie Albano, Ruth-Ann Gordon, Charles Leduc, Natasha Rekhtman, Bianca Harris, Jedd D. Wolchok, Michael A. Postow, and Matthew D. Hellmann, Memorial Sloan Kettering Cancer Center; Jamie E. Chaft, Neil H. Segal, Margaret K. Callahan, Alexander M....
ORCID
Venue
Journal of Clinical Oncology
Publisher
American Society of Clinical Oncology (ASCO)
Published
2017-03-01
Volume
35
Issue
7
Pages
709-717
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
DOI
10.1200/jco.2016.68.2005
PMC
PMC5559901
OpenAlex
W2522337762
Cited by
1,215
References
36
Citations by year
2026: 102 · 2025: 118 · 2024: 124 · 2023: 122 · 2022: 126 · 2021: 147 · 2020: 173 · 2019: 112 · 2018: 112 · 2017: 73 · 2016: 1
FWCI
53.50
Type
journal article
Language
en
Update notices
correction (2017-08-01)
Open access
Locations
  • Journal of Clinical Oncology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Bristol-Myers Squibb
  • Celgene
  • National Cancer Institute (P30CA008748)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
Keywords
pneumonitis, immune checkpoint inhibitors, anti-PD-1 therapy, PD-L1 blockade, CTLA-4 blockade, immune-related adverse events, melanoma, non-small cell lung cancer, solid tumors, combination immunotherapy, radiological features, pathological features, treatment discontinuation, immunosuppression, prognostic factors
MeSH terms
Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Humans, Immunotherapy, Middle Aged, Neoplasms, Pneumonia, Treatment Outcome, Membrane Transport Proteins, B7-H1 Antigen, Programmed Cell Death 1 Receptor

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