P017 Immunotherapy related hepatotoxicity: a retrospective, descriptive analysis of patients treated with combination immunotherapy at a single centre

Abstract

<h3></h3> Immune checkpoint inhibitors have transformed the treatment of various cancers including metastatic melanoma. Immune checkpoints are regulatory mechanisms which modulate the immune system and prevent overwhelming autoimmune attack. This may be exploited by certain tumour types, leading to attenuation of T cell activation and thus expansion and growth of tumour cells. Blockade of pathways including CTLA-4, PD-1 and PDL-1 has emerged as an approach to remove this inhibitory immune checkpoint mechanism and allow host to mount immune responses against tumour cells.^{1 2} Immune related adverse events (irAEs) are important, as high grade toxicities may require corticosteroids and discontinuation of treatment. The incidence of high grade irAEs is greater with CTLA-4 inhibitors (ipilimumab) than PD-1 inhibitors (nivolumab), and risk is increased further in combination (Ipi/Nivo). Ipi/Nivo induced hepatitis is an important irAE occurring in 17.6% patients (any grade) with 8.3% experiencing grade 3/4 hepatitis, based on previous trial data.^3–6 Continued analysis of real-world data is important to better establish the natural history of immunotherapy related hepatitis. Lancashire Teaching Hospitals is the tertiary cancer centre for Lancashire and South Cumbria. Electronic records, biochemistry results and oncology prescribing databases were retrospectively analysed for 68 patients treated with Ipi/Nivo between August 2016 and October 2020. 36 (52.9%) patients experienced hepatotoxicity (any grade) with n= 11 (16.2%) patients developing grade 3 or 4 hepatitis. The median time of onset of hepatotoxicity from the first dose (all grades) was 40 days (range 8–322). Amongst patients who experienced hepatotoxicity, the proportion treated with intravenous, oral or nil corticosteroids was 47.2%, 38.9% and 13.9% respectively. 4 patients required escalation to MMF and 1 patient needed tacrolimus as a third agent. Of patients who developed hepatotoxicity, n=29 had combination treatment discontinued prior to completion of 4 cycles. 15 patients were re-challenged with single agent nivolumab. Of the patients re-challenged, n=9 (60%) did not experience any further hepatotoxicity. This data demonstrated Ipi/nivo induced hepatitis occurring at a higher rate than in reported studies. This highlights the importance in monitoring real world data with novel anti-cancer therapies however, larger collaborative datasets are required. In addition, further comparative effectiveness research regarding treatment with oral vs intravenous corticosteroids will be important. 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