Eosinophil as a biomarker for diagnosis, prediction, and prognosis evaluation of severe checkpoint inhibitor pneumonitis

Abstract

IntroductionCheckpoint inhibitor pneumonitis (CIP) is a common serious adverse event caused by immune checkpoint inhibitors (ICIs), and severe CIP can be life-threatening. We aimed to investigate the role of peripheral blood cells in diagnosis, prediction, and prognosis evaluation for all and severe CIP.Materials and methodsPatients with lung cancer receiving ICIs were enrolled in this retrospective study. Baseline was defined as the time of ICI initiation, endpoint was defined as the time of clinical diagnosis of CIP or the last ICI treatment, and follow-up point was defined as 1 week after CIP. Eosinophil percentages at baseline, endpoint, and follow-up point were shortened to “Ebas”, “Eend and “Efol”, respectively.ResultsAmong 430 patients included, the incidence of CIP was 15.6%, and severe CIP was 3.7%. The Eend/Ebas value was lower in patients with CIP (p = 0.001), especially severe CIP (p = 0.036). Receiver operating characteristic curves revealed that Eend/Ebas could serve as a biomarker to diagnose CIP (p = 0.004) and severe CIP (p < 0.001). For severe CIP, the eosinophil percentage declined before the symptoms appeared and CT diagnosis. The eosinophil percentage significantly elevated at the follow-up point in the recovery group but not in the non-recovery group. The CIP patients with Efol/Ebas ≥1.0 had significantly prolonged overall survival (p = 0.024) and after-CIP survival (AS) (p = 0.043). The same results were found in severe CIP but without a statistical difference.ConclusionsEosinophil percentage was associated with the diagnosis, prediction, and prognosis of CIP and severe CIP.

Immune-related pulmonary toxicities of checkpoint inhibitors in non-small cell lung cancer: Diagnosis, mechanism, and treatment strategies

“…Pavan et al found that elevated neutrophil-to-lymphocyte ratio (NLR) and platelet-tolymphocyte ratio (PLR) might be associated with the occurrence, severity, and subsequent prognosis of iRAEs (37). In another study, researchers found that the decrease in eosinophils was closely correlated with the CIP, especially for the high grades CIP (38). Importantly, the ratio of the percentage of eosinophils to the percentage of eosinophils at the onset of CIP is an essential marker for distinguishing CIP from pneumonia caused by bacterial infection and cancer progression (39).…”

Uncovering the flip side of immune checkpoint inhibitors: a comprehensive review of immune-related adverse events and predictive biomarkers

“…Patients with IAP had low eosinophil percentages at endpoint (Eend)/ baseline (E bas ) values (p = 0.001), especially for severe IAP (p = 0.036). In addition, E end /E bas values performed well in the diagnosis of severe IAP (AUC:0.800, p<0.001), indicating that eosinophil percentage correlates with the diagnosis, prediction and prognosis of IAP [143]. A meta-analysis of 17 RCTs with 2758 patients revealed that individuals with NSCLC and interstitial lung disease (ILD) had a higher likelihood of developing pneumonia after immunotherapy.…”

Anti‑PD‑1/PD‑L1 and anti‑CTLA‑4 associated checkpoint inhibitor pneumonitis in non‑small cell lung cancer: Occurrence, pathogenesis and risk factors (Review)

“…Recent studies have demonstrated that eosinophils may be involved in CIP. By analyzing the peripheral blood of 430 lung cancer patients treated with ICIs, Li et al ( 67 ) observed that eosinophils in the CIP group (n=67) differed at the beginning of ICI treatment ( E bas ), diagnosis of CIP ( E end ), and 1 week after CIP diagnosis ( E fol ). The E end / E bas ratio signally decreased and was correlated with the severity of CIP.…”

“…IL-1β is a critical pro-inflammatory factor, primarily synthesized and secreted by monocytes and macrophages. High levels of IL-1β in the serum can promote acute lung injury and pulmonary fibrosis ( 67 , 81 ). Elevated IL-1β at baseline and early in anti-PD-1 therapy (1-6 weeks after anti-PD-1 therapy) is predictive of irAEs ( 70 ).…”