Immune related liver toxicity, management, and outcomes in ICI treated patients with advanced or metastatic cancers.

Abstract

2599 Background: The impact of hepatic immune-related adverse events (HirAEs) and their management (mgmt) on clinical outcomes in patients receiving immune checkpoint inhibitors (ICI) has not been fully examined. We aimed to evaluate the association between HirAEs, their mgmt, and overall survival (OS) in ICI-treated cancer patients. Methods: Data were drawn from the Flatiron Health Research Database, an EHR-based database representing 280+ U.S. community oncology practices. Adults with advanced non-small cell lung cancer (aNSCLC), advanced melanoma (aMel), or metastatic renal cell carcinoma (mRCC) who initiated ICI between 1/1/16 - 12/31/20 were included and followed from ICI initiation to death, loss to follow-up, or end of the study period (12/31/2021). CTCAE Grade 2 or higher HirAEs and mgmt actions (immunosuppression using corticosteroids or other immunosuppressants, ICI-regimen holds, ICI-regimen discontinuations) and hospitalizations were curated from unstructured data. Cox regression was used to evaluate the association between HirAEs, their mgmt (both as time-varying covariates) and OS adjusting for baseline characteristics such as line of therapy and corticosteroid use. The earliest HirAE per patient was examined in OS analysis. Results: The study included 529 aNSCLC, 557 aMel, and 431 mRCC patients. For aNSCLC, aMel, and mRCC, respectively, 23.4%, 41.5%, and 30.9% experienced at least one HirAE, with a median time to onset of 59, 60, and 63 days. Among all HirAEs, elevated liver enzymes were the most common (72.9% in mRCC to 76.6% in aMel), followed by hepatitis (8.3% in aNSCLC to 12.6% in aMel). Immunosuppression was used to treat HirAEs in 47.6%, 57.6%, and 38.3% of aNSCLC, aMel, and mRCC patients with HirAEs. In aNSCLC, aMel, and mRCC, respectively, median survival was 12.7, 52.2, and 25.5 months and HirAEs were associated with a higher risk of all-cause mortality than no HirAEs [HR (95%CI): 1.8 (1.3-2.2); 1.4 (1.0-1.8); 1.3 (1.0-1.8)]. In mRCC, ICI-regimen holds and discontinuations were associated with a higher risk of all-cause mortality than immunosuppression alone (HR≥4.0; P≤0.05). In aNSCLC, HirAEs that led to hospitalization were associated with a higher risk of all-cause mortality regardless of HirAE mgmt (HR: 6.2; P < 0.01). In aMel HirAE mgmt was not associated with OS. Conclusions: ICI-related HirAEs were associated with higher mortality in aNSCLC, aMel, and mRCC. HirAE mgmt impacted OS differently across cancer types, highlighting the need for tailored, timely, and multidisciplinary mgmt strategies in the ambulatory care setting, especially for cancers with poorer prognosis.