962 Immune related hepatitis is associated with improved survival in patients with melanoma and liver metastases
Year: 2026
Type: conference-abstract
Abstract: Background The expanded use of immune checkpoint inhibitors (ICIs) has led to the increased incidence of immune-related adverse events (irAEs), but the relationship between anti-tumor responses and irAEs remains unclear. Notably, metastatic spread to a specific organ has been associated with an increased likelihood of developing an irAE in that same organ. In patients with metastatic melanoma, liver metastases are associated with poor responses to ICIs. In unselected patient populations, the development of immune related hepatitis (irHepatitis) has not been associated with ICI responses, but the prognostic impact of irHepatitis on survival in patients with liver metastases is unknown.Methods We conducted a retrospective, single-center study of patients with melanoma who received first-line immunotherapy in the metastatic or unresectable setting and had radiographic evidence of liver metastases present at initiation of first-line immunotherapy or diagnosed within 6 months of treatment initiation. Patients were eligible regardless of any prior adjuvant or neoadjuvant therapy. irAEs of interest included irHepatitis and biopsy-proven luminal gastrointestinal (GI) irAEs, tracked from first-line treatment initiation to last follow-up. The primary outcome of interest was overall survival (OS), assessed using a 5-year landmark survival analysis. Survival analysis was performed using the Kaplan-Meier method with the log-rank test, and 2x2 comparisons were assessed using Fisher’s exact test.Results A total of 275 patients with metastatic or unresectable melanoma met inclusion criteria. The cohort was composed of cutaneous melanoma (n = 200, 72.7%), uveal (n = 51, 18.5%), acral (n = 14, 5.1%), and mucosal (n = 10, 3.6%) subtypes. First-line regimens included aPD1 (n = 104), aCTLA4 (n = 27), aPD1/aCTLA4 (n = 130), aPD1/aLAG3 (n = 11), and aPD1/aCTLA4/aLAG3 (n = 3). irHepatitis occurred in 36 patients (13.1%), of whom 25/36 (69.4%) were biopsy-proven, while 239 patients (86.9%) did not develop irHepatitis. Biopsy-proven luminal GI irAEs occurred in 66/275 patients (24.0%). Biopsy-proven luminal GI irAEs occurred in 36.1% (13/36) of patients with irHepatitis compared to 22.2% (53/239) without irHepatitis (p = 0.092). The development of irHepatitis was significantly associated with improved overall survival ( figure 1, p < 0.001). Conversely, in a subgroup analysis restricted to patients who did not develop irHepatitis, survival did not differ between those who developed luminal GI irAEs and those who did not (figure 2, p = 0.423).Conclusions In this real-world population of patients with melanoma and liver metastases, the development of irHepatitis was associated with improved survival outcomes, while luminal GI irAEs were not associated with prolonged survival. These findings suggest that irHepatitis may be associated with favorable immune activity against liver metastases.Ethics Approval Study obtained ethics approval and participants gave informed consent before taking part in the study. IRB Number: 2017P000501 (Mass General Brigham/MGB)Abstract 962 Figure 1Overall survival, Kaplan-Meier figures, log rank test. Survival analysis comparing irHepatitis-positive versus irHepatitis-negative patients across the entire cohort (n = 275)Abstract 962 Figure 2Overall survival, Kaplan-Meier figures, log rank test. Subgroup survival analysis restricted to irHepatitis-negative patients (n = 239), comparing those with biopsy-proven luminal GI irAEs versus those without
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225164267