Multiorgan immune-related adverse events during treatment with atezolizumab

Background: Immune-related adverse events (irAEs) are known to occur in patients with cancer who are treated with immune checkpoint inhibitors. However, limited literature exists on the incidence, time of onset, and risk factors for irAEs, particularly those affecting multiple organs, associated with anti-PD-L1 inhibitors. Methods: A post hoc pooled analysis was conducted using individual patient data from atezolizumab monotherapy arms of 4 non-small cell lung cancer clinical trials. Incidence, clinical patterns, outcomes, and risk factors were investigated of selected organ-specific and multiorgan irAEs during treatment using the anti-PD-L1 inhibitor atezolizumab. Results: From a total of 1,548 patients, 730 irAE episodes were reported in 424 patients (27%). Skin irAEs were the most common (42%), followed by laboratory abnormalities (27%) and endocrine (11.6%), neurologic (7.6%), and pulmonary (6.2%) irAEs. A total of 84 patients (5.4%) had multiorgan irAEs, 70 had 2, 13 had 3, and 1 had 4 different organs affected. "Skin plus" or "laboratory plus" were the most common irAE multiorgan clusters. Patients with multiorgan irAEs were more likely to be white and have a good performance status, a lower baseline neutrophil-lymphocyte ratio, and a good or intermediate lung immune prognostic index score. Multiorgan irAEs were also associated with improved overall survival (hazard ratio, 0.47; 95% CI, 0.28-0.78; P,.0001) but not with progression-free survival (hazard ratio, 0.92; 95% CI, 0.62-1.35; P5.74) compared with the cohort with no irAEs. Conclusions: Multiorgan irAEs occurred in 5.4% of patients treated with atezolizumab in non-small cell lung cancer trials. Future trials should consider routine reporting of data on multiorgan toxicities in addition to organ-specific toxicities.