Eosinophilia during treatment of immune checkpoint inhibitors (ICIs) to predict succeeding onset of immune-related adverse events (irAEs).

Abstract

e14110 Background: ICIs such as anti-PD-1/-L1 Inhibitor and anti-CTLA-4 Inhibitor have been used in many types of cancer, and irAEs occur in a considerable proportion of patients. Predictive biomarkers could help us to manage irAEs promptly. Methods: We retrospectively analyzed the consecutive patients treated with nivolumab, pembrolizumab, atezolizumab or ipilimumab, not used as investigational drugs, between March 2015 and December 2018 based on the electric medical records in our institution. We evaluated the relationship between clinical and laboratory factors (gender, age, body mass index, lymphocyte-to-monocyte ratio and eosinophilia) and the occurrence of irAEs using univariate and multivariate analyses. Eosinophilia was defined as absolute eosinophil count over 500/mm3 at least once between initiation of treatment and the occurrence of irAEs. We graded irAEs according to CTCAE v. 5.0. Results: Among 139 patients analyzed in this study, 136, 13 and 6 patients were treated with PD-1, PD-L1 and CTLA-4 inhibitors, respectively (cumulative total of 155 patients). This study included non-small cell lung cancer (n = 78; 56.1%), renal cell carcinoma (n = 17; 12.2%), melanoma (n = 16; 11.5%), gastric cancer (n = 15; 10.8%), Hodgkin lymphoma (n = 7; 5.0%), urothelial carcinoma (n = 3; 2.2%), head and neck carcinoma (n = 3; 2.2%) and mesothelioma (n = 1; 0.7%). Any grade and grade 3-5 irAEs occurred in 60 (38.7%) and 23 (14.8%) cumulative patients, respectively. The most common irAEs in any grade were endocrine disorders including thyroid dysfunction and adrenal insufficiency (n = 21) and skin disorders (n = 20). Eosinophilia occurred in 43 cumulative patients (27.7%). Eighteen patients out of them had eosinophilia from baseline. Among the clinical and laboratory factors, only eosinophilia was significantly associated with the occurrence of any grade of irAEs in both univariate (p = 0.0193) and multivariate (p = 0.0464) analysis. Notably, endocrine irAEs were significantly related to eosinophilia (p = 0.0287). Conclusions: Eosinophilia after the initiation of treatment with ICIs predicts succeeding onset of irAEs.

Hypereosinophilia is a predictive biomarker of immune checkpoint inhibitor-induced hypopituitarism in patients with renal cell carcinoma

“…These biochemical changes are not so common in ICI-induced hypopituitarism; conversely, hypereosinophilia was observed before the onset of hypopituitarism [ 15 ]. Several studies have reported that eosinophilia is associated with the occurrence of any grade of irAEs [ 16 – 18 ]. Thus, the present study aimed to evaluate whether hypereosinophilia can be used as a useful early clinical biomarker of ICI-induced hypopituitarism in patients with RCC.…”

Pan-Cancer Analysis Reveals Alternative Splicing Characteristics Associated With Immune-Related Adverse Events Elicited by Checkpoint Immunotherapy

“…Innate immune cells can mediate irAE development likely both in cooperation with and independent of adaptive immune cells ( Lee et al, 2021 ). Studies have reported associations of irAEs with the recruitment of CD14 + CD16 + monocytes ( Curry et al, 2019 ), the presence of eosinophilia ( Kizawa et al, 2019 ), increased neutrophil/lymphocyte ratio (NLR) ( Drobni et al, 2020 ), as well as NK cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) reactions ( Kelly et al, 2018 ). In addition to the innate immunity, seven genes related to the adaptive immune response also underwent alternative splicing and that were highly correlated with irAE risk ( Figure 4A ).…”

Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA

“…Bernard-Tessier et al reported an increased eosinophil count after treatment of patients with antibodies directed against PD-1 or its ligand PD-L1 while other immune cells remained unaffected [43]. Hypereosinophilia has also been discussed to be a parameter for the onset of immune-related adverse events (irAEs) [44]. These inflammatory side effects are associated with checkpoint inhibitor therapy [45].…”