Clinical and Hematological Predictors of High-Grade Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors

Abstract

Background: Life-threatening immune-related adverse events (irAEs) that require hospital admission are not uncommon in patients treated with immune checkpoint inhibitors (ICIs). The clinical and hematological parameters are attractive biomarkers as potential predictors of irAE.Methods: This is a retrospective study of patients with melanoma and lung cancer treated with ICIs between 2015 and 2019 at the University of South Alabama Mitchell Cancer Institute. Fisher's exact test, Pearson Chi-squared test, log-rank test, and Cox proportional hazard model were used to evaluate clinical and hematological parameters as possible predictors of irAE. Results:The cohort consisted of 160 patients treated with at least two doses of ICI, of which 54 (33.8%) patients had melanoma and 106 (66.3%) had lung cancer. Incidence of irAE did not have any bearing on the overall survival (OS) or progression-free survival (PFS) of the cohort. The clinical factors associated with irAE were dual-agent therapy (ipilimumab/nivolumab combination) and high disease burden (≥ 2 metastatic sites). The irAE-group had a lower mean platelet-to-lymphocyte ration (PLR, 200 vs. 257, P = 0.04). Although not statistically significant at the level of 0.05, other factors such as type of cancer (lung cancer > melanoma (P = 0.06)), stage at treatment (stage IV > stage II and III disease (P = 0.06)), and higher absolute lymphocyte counts (P = 0.07) showed a considerable association with irAE and warrants further review with different patient data.Conclusions: Irrespective of ICI used to treat lung cancer and melanoma, patients with high disease burden and dual-agent ICI therapy were more prone to irAE. The only hematological parameter that may predict the incidence of irAE is low baseline PLR.

Risk Factors and Biomarkers for Immune-Related Adverse Events: A Practical Guide to Identifying High-Risk Patients and Rechallenging Immune Checkpoint Inhibitors

“…Early studies could not establish any causal relationships with demographic and social factors such as age, gender, race, smoking, or diabetes ( 69 , 70 ). Even in our study on hospital-requiring irAEs in lung cancer (NSCLC and small cell) and MM patients, demographics were not significantly different in irAE groups from non-irAE groups ( 24 ). Another study out of Japan where the study population included 86 patients with NCLC, renal cell carcinoma (RCC), UC, Microsatellite instability-high (MSI-H) small bowel cancers also had similar conclusions ( 71 ).…”

“…Disease burden also seems to play a role in the incidence of irAE. In our study, MM and lung cancer patients with ≥2 metastatic sites had a higher risk of severe irAE ( 24 ). In a small retrospective review on NSCLC patients (N=42), more irAE were among patients with high tumor burden (defined as the sum of the unidimensional diameters of up to five target lesions) ( 62 ).…”