Dataset Information

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.

SUBMITTER: Manne A

PROVIDER: S-EPMC8166288 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Although immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with many advanced malignancies, only 15-60% of patients respond, leaving a broad swath of patients who do not derive benefit. Identifying biomarkers to optimally identify patients who will benefit from ICIs is a major research focus for the oncology community. Thus far, predictive biomarker research has focused on tumor signatures such as microsatellite instability, programmed death-ligand 1 (PD-L1) expression and tumor mutational burden; clinical biomarkers have been far less studied. One potential clinical biomarker for ICI response in patients is immune-related adverse event (IRAE) onset.IRAEs are thought to represent bystander effects from activated T-cells and it is plausible that patients responding to ICIs would have greater likelihood of autoimmune toxicities (e.g. due to a more competent/treatment-responsive immune system, or cross-reactivity between tumor and host tissue). Earlier studies in melanoma patients however, suggested no association between IRAE onset and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody efficacy. In contrast, a growing body of literature suggests IRAE onset is predictive of anti-programmed cell death protein 1 (PD-1) and anti-PD-L1 antibody response across a variety of solid tumors. Most of these studies report that patients who experienced IRAEs demonstrate marked improvements in progression-free survival, overall survival and overall response rate compared to those lacking toxicity.Key questions regarding the association between IRAE onset and ICI efficacy remain. The most pertinent of these involve whether the association is only relevant for patients treated with anti-PD-1 and anti-PD-L1 antibodies and whether IRAE site, severity, timing of onset and management influence ICI efficacy. Herein, we discuss the seminal studies which have begun to address these questions and have shaped the narrative about the predictive value of IRAE onset for patients on ICIs, in this review.

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