Enasidenib, an inhibitor of mutant IDH2 proteins, induces durable remissions in older patients with newly diagnosed acute myeloid leukemia Journal Article

   

Authors:	Pollyea, D. A.; Tallman, M. S.; de Botton, S.; Kantarjian, H. M.; Collins, R.; Stein, A. S.; Frattini, M. G.; Xu, Q.; Tosolini, A.; See, W. L.; MacBeth, K. J.; Agresta, S. V.; Attar, E. C.; DiNardo, C. D.; Stein, E. M.
Article Title:	Enasidenib, an inhibitor of mutant IDH2 proteins, induces durable remissions in older patients with newly diagnosed acute myeloid leukemia
Abstract:	Older adults with acute myeloid leukemia (AML) who are not fit for standard chemotherapy historically have poor outcomes. Approximately 12–15% of older patients with AML harbor isocitrate dehydrogenase 2 (IDH2) gene mutations. Enasidenib is an oral inhibitor of mutant IDH2 proteins. Among 39 patients with newly diagnosed mutant-IDH2 AML who received enasidenib monotherapy in this phase I/II trial, median age was 77 years (range 58–87) and 23 patients (59%) had had an antecedent hematologic disorder. The median number of enasidenib treatment cycles was 6.0 (range 1–35). The most common treatment-related adverse events were indirect hyperbilirubinemia (31%), nausea (23%), and fatigue, decreased appetite, and rash (18% each). Treatment-related grade 3–4 cytopenias were reported for eight patients (21%); there was no treatment-related grade 3–4 infections. Twelve patients achieved a response (overall response rate 30.8% [95% CI 17.0%, 47.6%]), including seven patients (18%) who attained complete remission. At a median follow-up of 8.4 months, the median duration of any response was not reached (NR). Median overall survival for all patients was 11.3 months (95% CI 5.7, 15.1), and was NR for responders. Oral, outpatient targeted treatment with enasidenib may benefit older adults with newly diagnosed mutant-IDH2 AML who are not candidates for cytotoxic regimens. © 2019, The Author(s).
Keywords:	adult; cancer survival; clinical article; treatment outcome; aged; survival rate; gene mutation; overall survival; constipation; fatigue; drug dose reduction; drug efficacy; drug safety; gastrointestinal hemorrhage; treatment duration; outcome assessment; gene; infection; multiple cycle treatment; anemia; leukopenia; nausea; thrombocytopenia; dna methylation; dyspnea; pneumonia; tumor lysis syndrome; drug response; peripheral edema; outpatient; hyperbilirubinemia; pericardial effusion; leukocytosis; cytopenia; tet2 gene; heart tamponade; asxl1 gene; decreased appetite; nras gene; idh2 gene; acute myeloid leukemia; dnmt3a gene; diastolic dysfunction; very elderly; human; male; female; priority journal; article; runx1 gene; enasidenib; srsf2 gene; stag1 gene
Journal Title:	Leukemia
Volume:	33
Issue:	11
ISSN:	0887-6924
Publisher:	Nature Publishing Group
Date Published:	2019-11-01
Start Page:	2575
End Page:	2584
Language:	English
DOI:	10.1038/s41375-019-0472-2
PUBMED:	30967620
PROVIDER:	scopus
PMCID:	PMC9724489
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85064174915&doi=10.1038%2fs41375-019-0472-2&partnerID=40&md5=1d3818bbfd5f6e244b4826fbd0c6edac
Notes:	Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/156903