Enasidenib vs conventional care in mutant-IDH2 relapsed/refractory acute myeloid leukemia: a randomized, phase 3 trial
Mené sur 319 patients atteints d'une leucémie myéloïde aiguë réfractaire ou récidivante et présentant une mutation au niveau du gène de l'IDH2 (âge médian : 71 ans), cet essai de phase III compare l'efficacité, du point de vue de la survie globale, et la toxicité de l'énasidénib (un inhibiteur de l'IDH2 dispensé par voie orale) et des soins conventionnels (azacitidine, cytarabine à faibles doses ou doses intermédiaires, soins de support), après l'échec de 2 ou 3 lignes thérapeutiques
This open-label, randomized, phase 3 trial (NCT02577406) compared enasidenib, an oral IDH2 inhibitor, with conventional care regimens (CCR) 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/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). Median age was 71 years. Median (range) enasidenib exposure was 142 days (3-1270) and CCR was 36 days (1-1166). 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. 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 months, 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 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.
Blood 2022