Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial

•EFS was meaningfully improved with enasidenib vs CCR; OS was confounded by early dropout and use of subsequent AML therapies.•Enasidenib provided meaningful morphologic and hematologic responses vs CCR in this heavily pretreated older R/R mutant-IDH2 AML population. [Display omitted] This open-labe...

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Published in:Blood 2023-01, Vol.141 (2), p.156-167
Main Authors: de Botton, Stéphane, Montesinos, Pau, Schuh, Andre C., Papayannidis, Cristina, Vyas, Paresh, Wei, Andrew H., Ommen, Hans, Semochkin, Sergey, Kim, Hee-Je, Larson, Richard A., Koprivnikar, Jaime, Frankfurt, Olga, Thol, Felicitas, Chromik, Jörg, Byrne, Jenny, Pigneux, Arnaud, Thomas, Xavier, Salamero, Olga, Vidriales, Maria Belen, Doronin, Vadim, Döhner, Hartmut, Fathi, Amir T., Laille, Eric, Yu, Xin, Hasan, Maroof, Martin-Regueira, Patricia, DiNardo, Courtney D.
Format: Article
Language:English
Subjects:
Aged
Cytarabine - therapeutic use
Humans
Isocitrate Dehydrogenase - genetics
Leukemia, Myeloid, Acute - drug therapy
Leukemia, Myeloid, Acute - genetics
Mutation
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Summary:•EFS was meaningfully improved with enasidenib vs CCR; OS was confounded by early dropout and use of subsequent AML therapies.•Enasidenib provided meaningful morphologic and hematologic responses vs CCR in this heavily pretreated older R/R mutant-IDH2 AML population. [Display omitted] 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
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.2021014901