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oai:recercat.cat:11351/98062024-12-13T09:37:15Zcom_2072_378070com_2072_378040col_2072_378092

Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial DE BOTTON, stephane Montesinos, Pau Schuh, Andre C. PAPAYANNIDIS, CRISTINA Vyas, Paresh Wei, Andrew H. Salamero, Olga 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 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 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. 2023-06-20T07:00:25Z 2023-06-20T07:00:25Z 2023-01-12 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion de Botton S, Montesinos P, Schuh A, Papayannidis C, Vyas P, Wei AH, et al. Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial. Blood. 2023 Jan 12;141(2):156–67. 1528-0020 https://hdl.handle.net/11351/9806 10.1182/blood.2021014901 35714312 000967645700001 http://hdl.handle.net/11351/9806 eng 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/ info:eu-repo/semantics/openAccess application/pdf application/pdf American Society of Hematology Scientia