IDH2 mutation + ALK fusion

Differentiation syndrome (DS) is a life-threatening condition associated with acute promyelocytic and acute myeloid leukemias (AML) treated with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO)...Treatment with ALK-inhibitor alectinib demonstrated good initial response followed by stable disease...Patient was switched to lorlatinib with clinical improvement...Patient was treated with high doses of IV dexamethasone followed by a slow taper for high suspicion of differentiation syndrome. After recovery, the patient was switched to standard chemotherapy regimen with carboplatin, pemetrexed, nivolumab and ipilimumab... Although uncommon in NSCLC at a prevalence of 0.4%-1.1%, IDH2 gain-of-function mutations and overexpression are correlated with poor disease outcomes due to prolonged tumor survival. IDH2 mutations are also found in subclonal populations with concurrent driver mutations such as KRAS and EGFR. Several studies in progress have suggested the potential anti-tumor activity of IDH2 inhibitors in the treatment of solid tumors.