Risk Factors for Refractory Immune Checkpoint Inhibitor-related Pneumonitis in Patients With Lung Cancer

Checkpoint inhibitor-related pneumonitis (CIP) is one of the most important immune checkpoint inhibitors side effects, and it is rare but fatal. Identifying patients at risk of refractory CIP before the start of CIP therapy is important for controlling CIP. We retrospectively analyzed the clinical data of 60 patients with lung cancer who developed CIP. Refractory CIP was defined as CIP with poor response to corticosteroid treatment, including CIP not relieved with corticosteroid administration or CIP recurrence during the corticosteroid tapering period. We analyzed clinical characteristics, peripheral blood biomarkers, treatment, and outcomes in nonrefractory and refractory CIP. Risk factors associated with refractory CIP were assessed. Among 60 patients with CIP, 16 (26.7%) had refractory CIP. The median onset time for patients with nonrefractory and those with refractory CIP was 16.57 (interquartile range [IQR], 6.82-28.14) weeks and 7.43 (IQR, 2.71-19.1) weeks, respectively. The level of lactate dehydrogenase (LDH) was significantly higher in the refractory CIP group at baseline (255 [222, 418] vs. 216 [183, 252], P=0.031) and at CIP onset (321.5 [216.75, 487.5] vs. 219 [198. 241], P=0.019). An LDH level >320 U/L at CIP onset was an independent risk factor of refractory CIP (odds ratio [OR], 8.889; 95% confidence interval [CI]: 1.294-61.058; P=0.026). The incidence of refractory CIP is high among patients with CIP. An increased LDH level at CIP onset is independently associated with refractory CIP. Monitoring LDH levels during immune checkpoint inhibitors treatment is recommended.