33P A literature review of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) caused by immune checkpoint inhibitors (ICIs), epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and multikinase inhibitors (MKIs)

Abstract

Stevens-Johnson syndrome (SJS)/ Toxic epidermal necrolysis (TEN) is the most severe type of drug eruption, characterized by blisters and generalized epidermolysis. Immune checkpoint inhibitors (ICIs), epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs), and multi-kinase inhibitors (MKIs) are three types of molucular therapy popularly used in advanced non-small cell lung cancer (NSCLC). The therapies can cause keratinocytes apoptosis, leading to SJS/TEN, which is not common but always life-threatening. We performed a retrospective analysis of case reports about ICIs, EGFR-TKIs, MKIs induced SJS/TEN by exploring PubMed, the Embase database, CNKI and WanFang. We analyzed 32 cases of SJS/TEN caused by ICIs (pembrolizumab, 11; nivolumab, 10; Ipilimumab + nivolumab, 5; Tislelizumab, 2; Toripalimab, 1; atezolizumab, 1; Camrelizumab, 1; Sintilimab+Toripalimab, 1). SJS/TEN could occur from 1 week to 5 months after initiation of ICIs, which was usually 1-2 cycles of treatment. SJS/TEN caused by ICIs is characterized by severe condition and high mortality. 11/32 patients were dead (pembrolizumab, 3; nivolumab, 3; Ipilimumab + nivolumab, 4; Sintilimab+Toripalimab, 1). Almost all patients who developed serious SJS/TEN had pre-symptoms, such as acneiform eruption, xerosis, pruritus. There were 8 cases of SJS/TEN associated with EGFR-TKIs (Osimertinib, 4; afatinib, 2; gefitinib, 1; vandetanib, 1). SJS/TEN usually occurred from 20 to 50 days of administration. The earliest occurrence time was 8 days, the latest occurrence was 78 days. There were 3 cases of MKIs related SJS/TEN (Regorafenib, 1; Sorafenib, 1; apatinib, 1). The apatinib-related case was treated with the combination of Toripalimab. No death associated with EGFR-TKIs and MKIs related SJS/TEN was reported. Compared with ICIS, EGFR-TKIs and MKIS related SJS/TEN is less common and mild, with well respond to steroid therapy and immunoglobulin and less deaths. It might be necessary to use anti-allergic agents before ICIs.