Risk factors for immune related adverse events: A retrospective study

Abstract

Background: Immunotherapy with checkpoint inhibition has gained high importance for oncological treatments with benefits in overall survival (OS). However these drugs are not harmless, and immune related adverse events (irAE) have been reported. We pretend to evaluate which patients (pts) are in risk for developing these. Methods: Retrospective evaluation of all pts treated with PD-1 and PD-L1 inhibitors for solid tumors in our center, during January 2015 and October 2018. A multivariate regression was made to determine potential risk factors for irAE. Significance was stablished at p<0,05. Statistical analysis was made with STATA. Results: 75 pts were included. Median age as 66 years (28-88y). 47 pts (62%) were male. 67 pts (90%) had metastatic disease. 48 pts (64%) were treated with nivolumab, 17 (22%) with pembrolizumab, 8 (10%) with durvalumab and 2 pts with atezolizumab. The most common diagnosis was non small cell lung cancer, with 53 pts (70%), of which 38 were adenocarcinomas. Urothelial cancer, hepatocellular carcinoma e renal cell cancer had 12%, 6% and 5%of the sample respectively. 31 (42%) pts had irAE. 20 (65%) had grade 2 or lower events, and 5pts had multiple irAE. The most common irAE were endocrine dysfunction, skin toxicity and pneumonitis, with 29%, 25% and 19% respectively. Of the 11 serious irAE (grade 3 or higher), the most common cause was pneumonitis with 5 cases. Median time of occurence was 3 weeks after the first treatment (0-52w). The multivariate regression showed higher likelihood of irAE in patients that were female, odds ratio (OR) of 3,72 (p=0,037, 95% confidence interval (CI95%) 1,15 -12,83); Lung adenocarcinoma, OR 3,94 (p=0,032, CI95% 1,12 -13,79), history of allergies, OR 17,04 (p=0,022; CI95%) 1,57 -191,55); history of autoimmune disease, OR 16,88 (p=0,002; CI95% 2,75 -103,48). There was no correlation between drug used, previous thoracic radiotherapy or previous steroid treatment. Conclusion: This study helped distinguish potential risk factors for irAE, like the female gender and history of allergies. Autoimmune disorders are already reported as risk factores. However the small sample isn't enough for us to draw accurate conclusions. More prospective trials are waranted in this setting.