Risk factors for immune‐related adverse events from anti‐PD‐1 or anti‐PD‐L1 treatment in an Asian cohort of nonsmall cell lung cancer patients

Abstract

Immune‐related adverse events (IrAEs) of immune checkpoint inhibitors (ICIs) can be serious and unpredictable. We examine the incidence rate and risk factors for IrAEs in an Asian cohort of nonsmall cell lung cancer (NSCLC) patients treated with immunotherapy. Between June 2014 and August 2020, we retrospectively analysed IrAEs in NSCLC patients treated with anti‐PD‐1 or anti‐PD‐L1 inhibitors at the National University Cancer Institute, Singapore. A Poisson regression model was used to estimate the effect of risk factors on incidence rate of any grade IrAEs. One hundred and forty‐one patients were enrolled. Median age was 63. Majority were male (67%) with Eastern Cooperative Oncology Group (ECOG) PS 0‐1 (77%). More than half (56%) received pembrolizumab. Eleven percent harboured epidermal growth factor receptor (EGFR) mutation. Eighteen percent received concomitant chemotherapy. Median number of cycles was 4, and median duration of treatment was 2.1 months. IrAEs were seen in 71 (50.4%) patients, with an incidence rate of 99 events per 1000 person‐months. Fatigue (25%), rash (10.5%) and pneumonitis (7.9%) were the most common IrAEs. Twenty out of 152 IrAEs (13.2%) were Grade 3 or higher in severity: most common being pneumonitis (5.3%), fatigue (3.3%) and transaminitis (1.3%). Multivariable analysis demonstrated that concomitant chemotherapy use, higher BMI and presence of EGFR mutation are significant predictors for IrAEs (P < .0001; P = .016; P = .007). Our findings can help guide risk stratification and monitoring of IrAEs among NSCLC patients on immunotherapy.

Peripheral absolute eosinophil count identifies the risk of serious immune-related adverse events in non-small cell lung cancer

“…The findings of Huang et al. in NSCLC are basically consistent with ours ( 29 ). Immune-related pneumonitis accounted for the highest proportion of grade 3-5 AEs, and elevated transaminases ranked second.…”

An open label, safety study of Asian patients with advanced non-small-cell lung cancer receiving second-line nivolumab monotherapy (CheckMate 870)

“… 28 Moreover, EGFR mutation, which is more prevalent in Asian patients with NSCLC, has been shown to increase the risk of immune-related AEs including pneumonitis. 29 Treatment-related pulmonary AEs were reported in 4%, 5%, and 7% of patients treated with nivolumab in CheckMate 017, 057, and 078 studies, respectively. In the present study, treatment-related select pulmonary AEs occurred in 4.4% and 5.9% of non-HBV and HBV-infected patients, respectively, and were implicated in two cases of treatment discontinuation and one death.…”

Pre-treatment Body Mass Index as a Predictive Biomarker for Immunotherapy Outcomes in Advanced Lung Cancer

“…Obesity was the sole predictor associated with an increased incidence of grade 3-4 irAEs (OR 11.9 [95% CI: 6.4-22.3]; p < 0.0001) (25). According to a publication, increased BMI is a signi cant predictor of irAEs (p = 0.016) in patients with NSCLC treated with anti-PD-1 or anti-PD-L1 inhibitors [13]. However, the incidence of irAEs among patients treated with anti-PD-1 and PD-L1 was superimposable regardless of BMI category (incidence of all grades irAEs: 31% for normal weight, 33% for overweight, and 36% for obese patients) (24).…”

“…A retrospective study found that baseline obesity is related to signi cantly increased ORR, progression-free survival (PFS), and overall survival (OS) in metastatic NSCLC patients with PD-L1 expression of ≥ 50% who received rst-line pembrolizumab, but not with chemotherapy (12). It has also been observed that BMI is related to immunotherapy toxicity (13).…”