TY - JOUR
T1 - Enasidenib, an inhibitor of mutant IDH2 proteins, induces durable remissions in older patients with newly diagnosed acute myeloid leukemia
AU - Pollyea, Daniel A.
AU - Tallman, Martin S.
AU - de Botton, Stéphane
AU - Kantarjian, Hagop M.
AU - Collins, Robert
AU - Stein, Anthony S.
AU - Frattini, Mark G.
AU - Xu, Qiang
AU - Tosolini, Alessandra
AU - See, Wendy L.
AU - MacBeth, Kyle J.
AU - Agresta, Samuel V.
AU - Attar, Eyal C.
AU - DiNardo, Courtney D.
AU - Stein, Eytan M.
N1 - Funding Information:
Acknowledgments This study was funded by Celgene Corporation and Agios Pharmaceuticals, Inc. The authors thank John Robinson of Celgene Corporation for assistance with data acquisition and analysis. Editorial support was provided by Sheila Truten and Kelly Dittmore (Medical Communication Company, Inc; Wynnewood, PA), funded by Celgene Corporation.
Funding Information:
Conflict of interest DAP receives research funding from Agios, AbbVie, and Pfizer, and serves on advisory boards for Celgene, Pfizer, Argenx, Agios, AbbVie, Agios, Celyad, and Gilead. MST received research funding from AROG, Cellerant, ADC Therapeutics, Celgene, Daiichi-Sankyo, and Orsenix, and participated in advisory boards for Orsenix, Biosight, and Daiichi-Sankyo. SdB received research funding from Agios Pharmaceuticals, Inc. and served on advisory boards for Agios Pharmaceuticals, Inc., Celgene, Pfizer, Novartis, Servier, Pierre Fabre, Bayer, Seagen, Carthagenetics, and Forma. HMK received research funding from Amgen, Ariad, Astex, BMS, Novartis, and Pfizer, and received honoraria from AbbVie, Amgen, Ariad, BMS, Immunogen, Orsinex, and Pfizer. RC received honoraria and received research funding from Agios Pharmaceuticals, Inc. ASS served on the speakers’ bureaus for Amgen and Celgene. MGF, QX, AT, and KJM are employed by and hold stock in Celgene. WLS is a contractor with Celgene. ECA and SVA are employed by and hold stock in Agios Pharmaceuticals, Inc. CDD is a consultant for Agios and Celgene, and served on the advisory board for Bayer, Karyopharm, MedImmune, and AbbVie. EMS has served on advisory boards for Astellas Pharma, Daiichi, Bayer, Novartis, Syros, Pfizer, PTC Therapeutics, AbbVie, Agios, and Celgene and has received research support from Agios, Celgene, Syros and Bayer.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41375-019-0472-2
DO - 10.1038/s41375-019-0472-2
M3 - Article
C2 - 30967620
AN - SCOPUS:85064174915
VL - 33
SP - 2575
EP - 2584
JO - Leukemia
JF - Leukemia
SN - 0887-6924
IS - 11
ER -