Sistema de Salut de Catalunya
Institut Català de la Salut
[de Botton S] Gustave Roussy, Université Paris-Saclay, Villejeuf, France. [Montesinos P] Hospital Universitari i Politecnic La Fe, Valencia, Spain. [Schuh AC] Princess Margaret Cancer Centre, Toronto, ON, Canada. [Papayannidis C] IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy. [Vyas P] Oxford Biomedical Research Centre and Oxford University Hospitals National Health Service Foundation Trust, Oxford, United Kingdom. [Wei AH] The Alfred Hospital, Melbourne, VIC, Australia. Monash University, Melbourne, VIC, Australia. [Salamero O] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2023-06-20T07:00:25Z
2023-06-20T07:00:25Z
2023-01-12
Enasidenib; Conventional care
Enasidenib; Atenció convencional
Enasidenib; Atención convencional
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 ≥60 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 = 158) or CCR (n = 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 = .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 = .008), TTF (median, 4.9 vs 1.9 months; HR, 0.53; P < .001), ORR (40.5% vs 9.9%; P <.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.
This work was supported by Celgene, a Bristol-Myers Squibb Company.
Article
Published version
English
Leucèmia mieloide aguda - Tractament; Leucèmia mieloide aguda - Aspectes genètics; Anomalies cromosòmiques; Medicaments antineoplàstics - Ús terapèutic; DISEASES::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myeloid, Acute; Other subheadings::Other subheadings::Other subheadings::/drug therapy; PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents; Other subheadings::Other subheadings::/therapeutic use; ENFERMEDADES::neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mieloide aguda; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos; Otros calificadores::Otros calificadores::/uso terapéutico
American Society of Hematology
Blood;141(2)
https://doi.org/10.1182/blood.2021014901
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
Articles científics - HVH [3440]
