{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T02:46:28Z","timestamp":1793933188712,"version":"4.8.0"},"reference-count":31,"publisher":"American Society of Hematology","issue":"2","license":[{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This open-label, randomized, phase 3 trial (NCT02577406) compared enasidenib, an oral IDH2 (isocitrate dehydrogenase 2) inhibitor, with conventional care regimens (CCRs) in patients aged \u226560 years with late-stage, mutant-IDH2 acute myeloid leukemia (AML) relapsed\/refractory (R\/R) to 2 or 3 prior AML-directed therapies. Patients were first preselected to a CCR (azacitidine, intermediate-dose cytarabine, low-dose cytarabine, or supportive care) and then randomized (1:1) to enasidenib 100 mg per day or CCR. The primary endpoint was overall survival (OS). Secondary endpoints included event-free survival (EFS), time to treatment failure (TTF), overall response rate (ORR), hematologic improvement (HI), and transfusion independence (TI). Overall, 319 patients were randomized to enasidenib (n\u00a0= 158) or CCR (n\u00a0= 161). The median age was 71 years, median (range) enasidenib exposure was 142 days (3 to 1270), and CCR was 36 days (1 to 1166). One enasidenib (0.6%) and 20 CCR (12%) patients received no randomized treatment, and 30% and 43%, respectively, received subsequent AML-directed therapies during follow-up. The median OS with enasidenib vs CCR was 6.5 vs 6.2 months (HR [hazard ratio], 0.86; P\u00a0= .23); 1-year survival was 37.5% vs 26.1%. Enasidenib meaningfully improved EFS (median, 4.9 vs 2.6 months with CCR; HR, 0.68; P\u00a0= .008), TTF (median, 4.9 vs 1.9 months; HR, 0.53; P\u00a0&amp;lt; .001), ORR (40.5% vs 9.9%; P &amp;lt;.001), HI (42.4% vs 11.2%), and red blood cell (RBC)-TI (31.7% vs 9.3%). Enasidenib safety was consistent with prior reports. The primary study endpoint was not met, but OS was confounded by early dropout and subsequent AML-directed therapies. Enasidenib provided meaningful benefits in EFS, TTF, ORR, HI, and RBC-TI in this heavily pretreated older mutant-IDH2 R\/R AML population.<\/jats:p>","DOI":"10.1182\/blood.2021014901","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T15:53:53Z","timestamp":1655481233000},"page":"156-167","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":128,"title":["Enasidenib vs conventional care in older patients with late-stage mutant-\n                    <i>IDH2<\/i>\n                    relapsed\/refractory AML: a randomized phase 3 trial"],"prefix":"10.1182","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8126-4942","authenticated-orcid":false,"given":"St\u00e9phane","family":"de Botton","sequence":"first","affiliation":[{"name":"1Gustave Roussy, Universit\u00e9 Paris-Saclay, Villejeuf, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3275-5593","authenticated-orcid":false,"given":"Pau","family":"Montesinos","sequence":"additional","affiliation":[{"name":"2Hospital Universitari i Politecnic La Fe, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre C.","family":"Schuh","sequence":"additional","affiliation":[{"name":"3Princess Margaret Cancer Centre, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8705-8333","authenticated-orcid":false,"given":"Cristina","family":"Papayannidis","sequence":"additional","affiliation":[{"name":"4IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3931-0914","authenticated-orcid":false,"given":"Paresh","family":"Vyas","sequence":"additional","affiliation":[{"name":"5Oxford Biomedical Research Centre and Oxford University Hospitals National Health Service Foundation Trust, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7514-3298","authenticated-orcid":false,"given":"Andrew H.","family":"Wei","sequence":"additional","affiliation":[{"name":"6The Alfred Hospital, Melbourne, VIC, Australia"},{"name":"7Monash University, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7628-8694","authenticated-orcid":false,"given":"Hans","family":"Ommen","sequence":"additional","affiliation":[{"name":"8Aarhus University Hospital, \u00c5rhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8129-8114","authenticated-orcid":false,"given":"Sergey","family":"Semochkin","sequence":"additional","affiliation":[{"name":"9Pirogov Russian National Research Medical University, Moscow, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4098-3366","authenticated-orcid":false,"given":"Hee-Je","family":"Kim","sequence":"additional","affiliation":[{"name":"10Catholic Hematology Hospital, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9168-3203","authenticated-orcid":false,"given":"Richard A.","family":"Larson","sequence":"additional","affiliation":[{"name":"11University of Chicago Comprehensive Cancer Center, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Koprivnikar","sequence":"additional","affiliation":[{"name":"12John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Frankfurt","sequence":"additional","affiliation":[{"name":"13Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicitas","family":"Thol","sequence":"additional","affiliation":[{"name":"14Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Medizinische Hochschule Hannover, Hanover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Chromik","sequence":"additional","affiliation":[{"name":"15Universit\u00e4tsklinikum Frankfurt, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Byrne","sequence":"additional","affiliation":[{"name":"16Nottingham University Hospitals Trust, Nottingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Pigneux","sequence":"additional","affiliation":[{"name":"17Bordeaux Haut-Leveque University Hospital, Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Thomas","sequence":"additional","affiliation":[{"name":"18Centre Hospitalier Universitaire de Lyon-Sud, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Salamero","sequence":"additional","affiliation":[{"name":"19Vall d\u2019Hebron Hospital Universitari, Vall d\u2019Hebron Institute of Oncology (VHIO), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Belen","family":"Vidriales","sequence":"additional","affiliation":[{"name":"20University Hospital of Salamanca and Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca, Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim","family":"Doronin","sequence":"additional","affiliation":[{"name":"21City Clinical Hospital No. 40, Moscow, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2116-5536","authenticated-orcid":false,"given":"Hartmut","family":"D\u00f6hner","sequence":"additional","affiliation":[{"name":"22Universit\u00e4tsklinikum Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir T.","family":"Fathi","sequence":"additional","affiliation":[{"name":"23Massachusetts General Hospital Cancer Center, Boston, MA"},{"name":"24Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7823-0004","authenticated-orcid":false,"given":"Eric","family":"Laille","sequence":"additional","affiliation":[{"name":"25Bristol Myers Squibb, Princeton, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yu","sequence":"additional","affiliation":[{"name":"25Bristol Myers Squibb, Princeton, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maroof","family":"Hasan","sequence":"additional","affiliation":[{"name":"25Bristol Myers Squibb, Princeton, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Martin-Regueira","sequence":"additional","affiliation":[{"name":"25Bristol Myers Squibb, Princeton, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9003-0390","authenticated-orcid":false,"given":"Courtney D.","family":"DiNardo","sequence":"additional","affiliation":[{"name":"26The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2023082419144129100_bib1","unstructured":"Cancer stat facts: leukemia - acute myeloid leukemia (AML). 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