Abstract
Background and aims: Current guidelines state that infliximab is contraindicated for the treatment of immune checkpoint inhibitor-related hepatitis (ir-hepatitis) due to the risk of inducing further liver damage. As this recommendation is largely based on the use of infliximab for rheumatologic diseases, we evaluated the efficacy and hepatotoxicity of infliximab in patients with steroid-refractory immune-related adverse events (irAEs). Methods: We retrospectively reviewed consecutive patients treated with infliximab for irAEs at Princess Margaret Cancer Centre. To assess hepatotoxicity, we compared the mean value of ALT, AST, and total bilirubin (BT) before and after infliximab treatment. We used logistic regression to assess factors associated with infliximab efficacy. Results: Between January 2010 and February 2019, 56 patients were identified. The median age of the patients was 63 (27–84) years. Colitis was the most frequent toxicity (66%), followed by pneumonitis (11%). Infliximab was used to treat ir-hepatitis in one patient. The median number of infliximab doses was 1 (1–3) and led to toxicity resolution in 43 (76%) patients. The mean ALT, AST, and BT levels before and after infliximab treatment were not statistically different. The patient treated for ir-hepatitis had a complete recovery, with no incremental liver toxicity. Conclusions: In this dose-limited setting, infliximab was effective in resolving irAEs and did not induce hepatotoxicity.
Highlights
IntroductionImmune checkpoint inhibitors (ICI), such as anti-programmed cell death 1 (anti-PD1), anti-programmed cell death-ligand 1 (anti-progressive disease (PD)-L1), and anti-cytotoxic T-Lymphocyte associated protein 4 (anti-CTLA-4) agents, act by disrupting inhibitory mechanisms of T-cell activation facilitating T-cell mediated cytotoxicity to cancer cells [1]
Immune checkpoint inhibitors (ICI), such as anti-programmed cell death 1, anti-programmed cell death-ligand 1, and anti-cytotoxic T-Lymphocyte associated protein 4 agents, act by disrupting inhibitory mechanisms of T-cell activation facilitating T-cell mediated cytotoxicity to cancer cells [1]
The most frequent toxicities treated with infliximab were colitis (37 cases; 66.1%) and pneumonitis (6 cases; 10.7%)
Summary
Immune checkpoint inhibitors (ICI), such as anti-programmed cell death 1 (anti-PD1), anti-programmed cell death-ligand 1 (anti-PD-L1), and anti-cytotoxic T-Lymphocyte associated protein 4 (anti-CTLA-4) agents, act by disrupting inhibitory mechanisms of T-cell activation facilitating T-cell mediated cytotoxicity to cancer cells [1]. Infliximab is recommended for most steroid-refractory irAEs, from relatively common conditions such as ir-colitis to other rarer irAEs [6], current guidelines recommend against its use for immunerelated hepatitis (ir-hepatitis) [2,3,7] This tenet originates from reports of infliximabinduced hepatotoxicity in patients receiving infliximab as a treatment for rheumatologic disorders or IBD [8,9]. Current guidelines state that infliximab is contraindicated for the treatment of immune checkpoint inhibitor-related hepatitis (ir-hepatitis) due to the risk of inducing further liver damage As this recommendation is largely based on the use of infliximab for rheumatologic diseases, we evaluated the efficacy and hepatotoxicity of infliximab in patients with steroid-refractory immune-related adverse events (irAEs). Conclusions: In this dose-limited setting, infliximab was effective in resolving irAEs and did not induce hepatotoxicity
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