Molecular and clinical features of hospital admissions in patients with thoracic malignancies on immune checkpoint inhibitors

Dan Zhao, Haiqing Li, Isa Mambetsariev, Chen Chen, Rebecca Pharaon, Jeremy Fricke, Angel R. Baroz, Prakash Kulkarni, Yan Xing, Erminia Massarelli, Marianna Koczywas, Karen L. Reckamp, Kim Margolin, Ravi Salgia

Research output: Contribution to journalArticlepeer-review

Abstract

Lung cancer patients undergoing systemic treatment with immune checkpoint inhibitors (ICIs) can lead to severe immune-related adverse events (irAEs) that may warrant immediate hos-pitalization. Patients with thoracic malignancies hospitalized at City of Hope while undergoing treatment with ICIs were identified. Pathology and available next-generation sequencing (NGS) data, including the programmed death-ligand 1 (PD-L1) status and clinical information, including hospitalizations, invasive procedures, and the occurrence of irAEs, were collected. Unpaired T-tests, Chi-square/Fisher’s exact test, and logistic regression were used to analyze our cohort. The overall survival (OS) was calculated and compared using univariate and multivariate COX models. Ninety patients with stage IV lung cancer were admitted after ICI treatment. Of those patients, 28 (31.1%) had documented irAEs. Genomic analyses showed an enrichment of LRP1B mutations (n = 5/6 vs. n = 7/26, 83.3% vs. 26.9%; odds ratio (OR) (95% confidence interval (CI): 13.5 (1.7–166.1); p < 0.05) and MLL3 mutations (n = 4/6, 66.7% vs. n = 5/26, 19.2%; OR (95% CI): 8.4 (1.3–49.3), p < 0.05) in patients with irAE occurrences. Patients with somatic genomic alterations (GAs) in MET (median OS of 2.7 vs. 7.2 months; HR (95% CI): 3.1 (0.57–17.1); p < 0.05) or FANCA (median OS of 3.0 vs. 12.4 months; HR (95% CI): 3.1 (0.70–13.8); p < 0.05) demonstrated a significantly shorter OS. Patients with irAEs showed a trend toward improved OS (median OS 16.4 vs. 6.8 months, p = 0.19) compared to hospitalized patients without documented irAEs. Lung cancer patients who required treatment discontinuance or interruption due to irAEs (n = 19) had significantly longer OS (median OS 18.5 vs. 6.2 months; HR (95% CI): 0.47 (0.28–0.79); p < 0.05). Our results showed a significant survival benefit in lung cancer patients hospitalized due to irAEs that necessitated a treatment interruption. Patients with positive somatic GAs in MET and FANCA were associated with significantly worse OS compared to patients with negative GAs.

Original languageEnglish (US)
Article number2653
JournalCancers
Volume13
Issue number11
DOIs
StatePublished - May 28 2021

Keywords

  • Admissions
  • Checkpoint inhibitors
  • Genomic alterations
  • Immune-related adverse events (irAEs)
  • Lung cancer
  • Next-generation sequencing
  • Overall survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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