Safety of Programmed Death–1 Pathway Inhibitors Among Patients With Non–Small-Cell Lung Cancer and Preexisting Autoimmune Disorders
Open accessAbstract
Purpose: Although programmed death (PD)-1 pathway inhibitors are now used in nearly all patients with advanced non–small-cell lung cancer (NSCLC), the large number of patients with NSCLC and concurrent autoimmune disease (AID) have been universally excluded from immunotherapy clinical trials. Therefore, the safety of PD-1 and PD-ligand 1 (PD-L1) inhibitors in patients with NSCLC and underlying AID is currently unknown. Methods: As part of a multi-institutional effort, we retrospectively collected clinicopathologic data from patients with NSCLC and a history of AID who received monotherapy with either a PD-1 or a PD-L1 (herein referred to as PD-[L]1) inhibitor. Qualifying AIDs included but were not limited to: rheumatologic, neurologic, endocrine, GI, and dermatologic conditions. Results: We identified 56 patients with NSCLC and an AID who received a PD-(L)1 inhibitor. At the time of treatment initiation, 18% of patients had active AID symptoms and 20% were receiving immunomodulatory agents for their AID. A total of 55% of patients developed an AID flare and/or an immune-related adverse event (irAE). Exacerbation of the AID occurred in 13 patients (23% of the whole cohort), four of whom required systemic corticosteroids. Immune-related adverse events occurred in 21 patients (38%). Among irAEs, 74% were grade 1 or 2 and 26% were grade 3 or 4; eight patients required corticosteroids for irAE management. PD-(L)1 therapy was permanently discontinued in eight patients (14%) because of irAEs. The overall response rate to immunotherapy in this population was 22%. Conclusion: In patients with NSCLC with AID treated with a PD-(L)1 inhibitor, exacerbation of AID occurred in a minority of patients. The incidence of irAEs was similar to reported rates in clinical trials where patients with AID were excluded. Adverse events were generally manageable and infrequently led to permanent discontinuation of immunotherapy.
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Several studies suggest thyroid dysfunction is associated with improved overall cancer survival, though the mechanism is not well understood.
“Several studies have suggested that thyroid dysfunction is associated with improved overall survival from a cancer standpoint, although the mechanism for this type of association is not well understood.39,40”
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- Authors
- Leonardi, G. C., Gainor, J. F., Altan, M., Kravets, S., Dahlberg, S. E., Gedmintas, L., Azimi, R., Rizvi, H., Riess, J. W., Hellmann, M. D., & Awad, M. M.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Awad, Mark M.
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2018-07-01
- Volume
- 36
- Issue
- 19
- Pages
- 1905-1912
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC6553840
- OpenAlex
- W2800772239
- Cited by
- 341
- References
- 17
- Citations by year
- 2026: 13 · 2025: 23 · 2024: 45 · 2023: 34 · 2022: 37 · 2021: 49 · 2020: 69 · 2019: 58 · 2018: 13
- FWCI
- 17.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P30CA008748)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Keywords
- PD-1 inhibitors, PD-L1 inhibitors, non-small cell lung cancer, autoimmune disease, immune-related adverse events, autoimmune disease flare, immunotherapy safety, corticosteroid use, treatment discontinuation, immunotherapy response
- MeSH terms
- Antineoplastic Agents, Immunological, Aged, Aged, 80 and over, Autoimmune Diseases, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Neoplasm Staging, Retrospective Studies, B7-H1 Antigen, Programmed Cell Death 1 Receptor
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