Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy

Abstract

Background: The phase 3 VIALE-A trial (NCT02993523) reported that venetoclax-azacitidine significantly prolonged overall survival compared with placebo-azacitidine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy. Herein, efficacy and safety of venetoclax-azacitidine are analyzed in the Japanese subgroup of VIALE-A patients.

Methods: Eligible Japanese patients were randomized 2:1 to venetoclax-azacitidine (N = 24) or placebo-azacitidine (N = 13). Primary endpoints for Japan were overall survival and complete response (CR) + CR with incomplete hematologic recovery (CRi). Venetoclax (target dose 400 mg) was given orally once daily. Azacitidine (75 mg/m2) was administered subcutaneously or intravenously on Days 1-7 of each 28-day cycle.

Results: Median follow-up was 16.3 months (range, 1.0-20.3). Median overall survival was not reached with venetoclax-azacitidine (hazard ratio 0.409 and 95% confidence interval: 0.151, 1.109); overall survival estimate was higher with venetoclax-azacitidine than placebo-azacitidine at 12 (67 and 46%) and 18 months (57 and 31%), respectively. CR and CRi rates were 67% with venetoclax-azacitidine and 15% with placebo-azacitidine. Most common any-grade adverse events were febrile neutropenia (79 and 39%), thrombocytopenia (54 and 77%), constipation (54 and 54%) and decreased appetite (54 and 38%) in the venetoclax-azacitidine and placebo-azacitidine arms, respectively. Only 1 patient in the venetoclax-azacitidine arm, and no patients in the placebo-azacitidine arm, had grade 4 febrile neutropenia that led to treatment discontinuation.

Conclusions: This Japanese subgroup analysis of VIALE-A demonstrates comparable safety and efficacy outcomes compared with the global study and supports venetoclax-azacitidine as first-line standard-of-care for Japanese treatment-naive patients with acute myeloid leukemia who are ineligible for intensive chemotherapy.

Keywords: Japan; VIALE-A; acute myeloid leukemia; azacitidine; venetoclax.

Figure 1

OS by treatment arm. ^aStratified by age (18 to <75, ≥75 years) and cytogenetic risk (intermediate, poor). Aza, azacitidine; CI, confidence interval; HR, hazard ratio; NR, not reached; OS, overall survival; Pbo, placebo; Ven, venetoclax.

Figure 2

Rates of CR and CR+CRi (a), and investigator-assessed event-free survival (b). ^aStratified by age (18 to <75, ≥75 years) and cytogenetic risk (intermediate, poor). Aza, azacitidine; CI confidence interval; CR, complete response; CRi, CR with incomplete blood count recovery; HR, hazard ratio; Pbo, placebo; Ven, venetoclax.

Figure 3

Proportion of patients with post-baseline transfusion independence. Transfusion independence was defined as a period of 56 days or more without transfusion. RBC, red blood cell.