Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia
Mené sur 145 patients atteints d'une leucémie myéloïde aiguë (âge médian : 74 ans), cet essai de phase Ib évalue la dose maximale tolérée, l'efficacité, du point de vue du taux de rémission, et la toxicité du vénétoclax en combinaison avec la décitabine ou azacitidine en traitement de première ligne
Venetoclax plus decitabine or azacitidine showed tolerable safety and favorable ORR (CR+CRi rate: 67%) in elderly AML patients.This novel combination regimen produced favorable responses in high-risk groups, such as age ≥75 years, poor cytogenetics, secondary AML. Older patients with acute myeloid leukemia (AML) respond poorly to standard induction therapy. BCL-2 overexpression is implicated in survival of AML cells and treatment resistance. We report safety and efficacy of venetoclax with decitabine or azacitidine from a large, multicenter, phase 1b dose-escalation and expansion study. Patients (N=145) were ≥65 years with treatment-naive AML ineligible for intensive chemotherapy. During dose escalation, oral venetoclax was administered at 400, 800, or 1200 mg daily in combination with either decitabine (20 mg/m2, days 1-5; intravenously [IV]) or azacitidine (75 mg/m2, days 1-7; IV or subcutaneously). In the expansion, 400 mg or 800 mg venetoclax with either hypomethylating agent (HMA) was given. Median age was 74 years, with poor-risk cytogenetics in 49% of patients. Common adverse events (>30%) included nausea, diarrhea, constipation, febrile neutropenia, fatigue, hypokalemia, decreased appetite, and decreased white blood cell count. No tumor lysis syndrome was observed. With a median time on study of 8.9 months, 67% of patients (all doses) achieved complete remission (CR) + CR with incomplete count recovery (CRi), with a CR+CRi rate of 73% in the venetoclax 400-mg + HMA cohort. Patients with poor-risk cytogenetics and those ≥75 years had CR+CRi rates of 60% and 65%, respectively. The median duration of CR+CRi (all patients) was 11.3 months and median overall survival (mOS) was 17.5 months; mOS has not been reached for the 400 mg venetoclax cohort. The novel combination of venetoclax with decitabine or azacitidine was effective and well tolerated in elderly patients with AML (https://clinicaltrials.gov/, NCT02203773).