Vorasidenib-Induced Acute Liver Injury.

BACKGROUND: Vorasidenib is a dual inhibitor of isocitrate dehydrogenase-1 and isocitrate dehydrogenase-2 used to treat patients with grade 2 astrocytoma or oligodendroglioma with either mutation. Vorasidenib has yet to be linked to cases of acute liver injury. AIMS: We describe 3 cases of severe acute liver injury with features of autoimmune hepatitis associated with vorasidenib and summarize 50 cases of vorasidenib-associated liver injury reported to the FDA. METHODS: This was a case series of 3 patients who developed severe acute liver injury during vorasidenib treatment. A search of the FDA Adverse Event Reporting System database identified 50 cases of suspected drug-induced liver injury from vorasidenib with usable information. RESULTS: Onset of elevated alanine aminotransferase activities (ALT) were 13, 31, and 2 weeks after vorasidenib initiation. Pattern of liver injury was hepatocellular; mean ALT 1748 U/L, bilirubin level 69.4 μmol/L, and R value 63.9. Despite discontinuation of vorasidenib, ALT continued to increase, and with histology showing centrizonal confluent necrosis, prompted initiation of 40-60 mg prednisone for possible drug induced autoimmune-like hepatitis. ALT normalized and steroids were tapered over 23, 3, and 7 months respectively. Patients remained in remission for 7-25 months after discontinuation of steroids. Among FAERS cases, mean latency to > 3× upper limit of normal ALT was 66 days, 9 were hospitalized, 7 received steroids, and 6 cases with sufficient data met Hy's Law criteria. CONCLUSION: Data suggest that vorasidenib-induced liver injury is hepatocellular with a subset that presents with autoimmune-like features which responds to a finite course of corticosteroids.