Clinical outcome of immune related hepatitis (IrHep) in patients with advanced melanoma (AM) treated with single agent or combination immune checkpoint inhibitors (ICIs)

Background: Immune related adverse events with single agent or combination ICIs are well described in patients (pts) with AM, but comprehensive clinical characterization of IrHep is still lacking. Here we report retrospectively collected clinical outcomes of IrHep in pts with AM treated with ICIs at Medstar Health Network hospitals. Methods: Pts with AM treated with ICIs (n = 189): ipilimumab (ipi) (n = 73), nivolumab (n = 17) or pembrolizumab (n = 48) (anti-PD1), or combination nivolumab plus ipilimumab (combo) (n = 51) were identified by pharmacy records. IrHep was defined as any elevation of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and graded in accordance with CTCAE v4.03. Pts with grade >2 ALT/AST elevation at baseline or rise attributed to causes other than IrHep were excluded. Highest grade ALT/AST was reported for each pt. Median time to resolution (MTR) to baseline was analyzed by KM analysis. Steroid use was captured from its initiation to for IrHep, till their discontinuation. Results: IrHep any grade was identified in 80 (42%) pts (19 (26%) ipi; 24 (37%) anti-PD-1; 37 (73%) combo). Median time to highest grade IrHep for ipi, anti-PD1, and combo groups was 8.78, 9.65 and 6.15 weeks respectively. IrHep grade ≥3 occurred in 3 (4%), 2 (3%) and 14 (27%) combo pts respectively. For IrHep grade ≥3 (n = 18), MTR was 5 weeks, median starting systemic steroid dose was 1mg/kg and median duration of steroid treatment was 5 weeks. For irHep grade 2 (n = 22), 32% (n = 7) pts were treated with systemic steroid (2 progressed to grade 3 and 5 resolved), 22.7% (n = 5) pts progress to grade 3-4 with treatment interruption, 22.7% resolved with treatment interruption and 22.7% resolved without treatment interruption. TTF failure for pts with/without IrHep was 5.1/12.4, 12.9/12.5 and NR/24.7 months with ipi, PD1 and combo pts respectively. Conclusions: In our real-world experience, IrHep was identified more frequently than in past AM studies, particularly in pts treated with combo. Pts with grade 3 ≥irHep resolved within 5 weeks with systemic steroids at starting dose of 1mg/kg. Pts with grade 2 irHep, one should not proceed with treatment unless they resolved to grade ≤1. Legal entity responsible for the study: Neil J Shah MD. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.