Efficacy and hepatotoxicity of Infliximab in resolving steroid-refractory immune-related adverse events (irAEs) in a real-world setting.

Abstract

e15227 Background: Infliximab is used to treat steroid-refractory immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICI). Current dogma holds that infliximab is contraindicated in immune hepatitis; steroid refractory disease should be managed with mycophenolate mofetil (MMF). This is based on anecdotal reports of infliximab-induced hepatotoxicity in patients with rheumatologic diseases who received multiple infusions of the drug. In this series of 56 consecutive cases of infliximab-treated patients, we assessed the efficacy of infliximab in resolving specific steroid-refractory irAEs and evaluated the risk of hepatotoxicity from this drug. Methods: We reviewed consecutive patients treated with infliximab for steroid-refractory irAE at a tertiary cancer center between January 2010 and February 2019. To judge hepatotoxicity, we used the Wilcoxon signed rank test to compare the mean value of ALT, AST and total bilirubin (BT) between 0-4 weeks before and after infliximab therapy. We compared factors associated with infliximab efficacy by logistic regression. A p value < 0.05 was considered statistically significant. Results: Mean age was 61.9 years. The majority had a diagnosis of melanoma (62%); 45% had a combination of two ICI before toxicity onset, of whom 73% received an anti-PD1 and an anti-CTLA-4. Colitis was the most common toxicity (66%), followed by pneumonitis (11%). Infliximab was used to treat immune related hepatitis (ir-hepatitis) in 1 patient (2%). Median number of infliximab doses was 1 (1-3), with resolution of toxicity in 76% of patients. Colitis was likely to resolve with infliximab in comparison to other irAE [OR 0.2(95% CI 0.05-0.73)]. Univariate logistic regression did not demonstrate statistical difference in toxicity outcome when ICI were given either as monotherapy (p = 0.3) or combination (p = 0.97). Mean BT, ALT and AST levels before and after infliximab were not statistically different (see table), with no evidence of infliximab-induced hepatotoxicity. The patient treated for ir-hepatitis had a complete recovery, with no further hepatotoxicity. Conclusions: Infliximab was effective in treating irAE and was not associated with hepatotoxicity in this dose-limited setting. Infliximab may be an alternative to MMF in steroid-refractory ir-hepatitis and should be tested prospectively in a randomized trial. [Table: see text]