Outcome and risk factor of immune‐related adverse events and pneumonitis in patients with advanced or postoperative recurrent non‐small cell lung cancer treated with immune checkpoint inhibitors

Abstract

BackgroundNon‐small cell lung cancer (NSCLC) patients with pre‐existing respiratory diseases have been excluded in clinical trials of immune checkpoint inhibitor (ICI) therapy, and it is unknown whether the same degree of response can be expected as that in patients without pre‐existing respiratory diseases and if they are associated with increased risk for various immune‐related adverse events (irAEs) and ICI pneumonitis. This study aimed to evaluate predictive factors of clinical response, prognostic factors, risk factors of irAEs, and ICI pneumonitis in NSCLC patients with or without pre‐existing respiratory diseases.MethodsWe conducted a retrospective study of 180 NSCLC patients who received ICI monotherapy of nivolumab, pembrolizumab, or atezolizumab from 1 January 2016 to 31 March 2019.ResultsA total of 119 patients had pre‐existing respiratory diseases, including 20 with pre‐existing idiopathic interstitial pneumonias (IIPs). A total of 85 patients experienced irAEs, of which ICI pneumonitis was the most frequent adverse event, occurring in 27 patients. Of the three patients who died from irAEs, all from ICI pneumonitis, two had pulmonary emphysema and one had pre‐existing IIP. In multivariate analyses, irAEs were associated with objective response rate (ORR) and favorable OS, and IIPs were associated with increased risk for ICI pneumonitis. However, IIPs were not associated with low ORR or poor OS.ConclusionsPre‐existing IIPs were a risk factor for ICI pneumonitis. However, this study showed that ICI therapy can be offered to patients with pre‐existing respiratory diseases with the expectation of the same degree of response as that in patients without pre‐existing respiratory diseases.Key pointsSignificant findings of the study: Pre‐existing IIPs were a risk factor for ICI pneumonitis, but objective response rate and prognosis of patients with IIPs were similar to those of other patients.What this study adds: In patients with pre‐existing IIPs, ICI pneumonitis should be noted. However, ICI therapy can be offered to patients with pre‐existing respiratory diseases with the expectation of the same degree of response as that in patients without pre‐existing respiratory diseases

Immune Checkpoint Inhibitor-Associated Pneumonitis in Non-Small Cell Lung Cancer: Current Understanding in Characteristics, Diagnosis, and Management

“…The current biomarkers are based on the mechanism of irAEs. Among the various biomarkers, Isono et al (176) recently found idiopathic interstitial pneumonias became the only risk factor of CIP in the multivariate Cox regression model. Therefore, the ability of these biomarkers to predict CIP should be investigated deeply.…”

Biomarkers and risk factors for the early prediction of immune-related adverse events: a review

“…In a study of irAEs in patients with NSCLC treated with PD-1 inhibitors, univariate and multivariate analyses of age (≥75 and <75) confirmed that age <75 was a risk factor for irAEs. 28 Another pooled analysis from four ICI trials reached the same conclusion and further confirmed that patients <65 years old are more likely to have grade 3 or 4 irAEs than patients ≥75 years old. 67 However, a pooled analysis of KEYNOTE-010 (NCT01905657), KEYNOTE-024 (NCT02142738), and KEYNOTE-042 (NCT02220894) studies showed that the incidence of irAEs did not differ between patients aged <75 years and ≥75 years.…”

“… 14 Studies have confirmed that increased white blood cell counts and relative lymphopenia are associated with grade 3/4 lung irAEs in patients with MM and treated with nivolumab; 26 high PD-L1 expression, increased eosinophil and monocyte counts, and decreased albumin and C-reactive protein (CRP) are risk factors for lung irAEs in NSCLC patients treated with ICIs. 28 Pneumonia irAEs can occur at any stage of treatment. The clinical symptoms mainly include dyspnea (53%), cough (35%) and fever (12%), 40 which are similar to respiratory tract infection symptoms and are easy to ignore.…”

“…Blood count is a routine clinical test item that includes much information, but the researches mainly focus on white blood cells, neutrophils, lymphocytes and platelets. The study of Isono et al 28 showed that in patients with NSCLC who were treated with PD-1 inhibitors, their white blood cell count and lymphocyte count were risk factors for the occurrence of irAEs. Pavan et al 51 collected baseline data on neutrophils/lymphocytes (NLR) and platelets/lymphocytes (PLR) of patients with aNSCLC treated with ICIs and found that low NLR (<3) and low PLR (<180) were significantly related to the occurrence of irAEs.…”

Checkpoint Inhibitor-Induced Colitis—A Clinical Overview of Incidence, Prognostic Implications and Extension of Current Treatment Options

“…A systematic review was also able to demonstrate the same finding [ 59 ]. Based on individual irAEs, a correlation has been shown for colitis [ 60 , 61 , 62 ] as well as for cutaneous adverse events and pneumonitis [ 63 , 64 , 65 , 66 , 67 , 68 , 69 ].…”