Dermatologic adverse events associated with IDH inhibitors ivosidenib and enasidenib for the treatment of acute myeloid leukemia. (December 2022)

• Record Type: Journal Article
• Authors: Parisi, Rose; Cowen, Emily A.; Stoll, Joseph R.; Zhu, Haoling; Dusza, Stephen; Pulitzer, Melissa P.; Stein, Eytan M.; Markova, Alina
• Is Part Of: Leukemia research. Volume 123(2022)
• Publication Date: 2022-12
• Subjects: Oncology -- Dermatology -- Adverse events -- Acute myeloid leukemia -- Targeted therapy -- Cutaneous differentiation syndrome; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2022.106970
• Languages: English
• ISSNs: 0145-2126

Abstract

Abstract: Two novel inhibitors of isocitrate dehydrogenase (IDHi), ivosidenib and enasidenib, significantly improve survival for AML patients with an IDH1 or IDH2 mutation, respectively; however, rash has been reported as a toxicity of IDHi. The objective of our study is to determine the incidence, grade, clinical, and histopathologic features of dermatologic adverse events (DAEs) secondary to IDHi. This study is a retrospective analysis of 169 patients who were treated with either ivosidenib or enasidenib as single agent or in combination with induction chemotherapy at Memorial Sloan Kettering Cancer Center from January 1, 2013 to April 1, 2021. DAEs thought to be possibly, probably, or definitely related to IDHi occurred in 55 of 169 patients [0.32, 95 % CI: 0.25 – 0.40]. Of a total 81 DAEs observed, the most common DAE types were inflammatory dermatoses (27 %); cutaneous vascular manifestations (8%); cutaneous infections (7%); and pruritus (2%). Notably, 50% of infections and 15.5% of rashes were high grade. Knowledge of these findings is critical to optimize the treatment and quality of life of patients with AML on IDHi. Highlights: To recognize cutaneous manifestations of IDH inhibitor therapies (enasidenib and ivosidenib). To understand the incidence and grading of IDHi dermatologic adverse events. To summarize dermatologic adverse events which prompt anticancer therapy interruption or discontinuation.