Phase II OPTI-AML trial: Azacitidine + 28- vs 14-day venetoclax in ND AML

The prospective, randomized, multicenter, phase II OPTI-AML trial (NCT03013998) evaluated azacitidine + 28-day venetoclax (AV28; n = 83) vs azacitidine + 14-day venetoclax (AV14; n = 86) for 2 cycles in older (≥60 years), intensive chemotherapy-ineligible patients with newly diagnosed acute myeloid leukemia (AML), irrespective of molecular subtype. The primary endpoint was complete remission (CR) rate achieved at any time with 2 cycles of therapy. Results were published in Blood by Borate et al.

Key data: After 2 cycles, CR rates were higher with AV28 (49.4%; 95% confidence interval [CI], 38.2–60.6) vs AV14 (43.0%; 95% CI, 32.4–54.2); however, AV14 did not meet the prespecified non-inferiority criterion. Composite CR (CRc) rates were also higher with AV28 vs AV14 (80.7% vs 68.6%); among responders, measurable residual disease (MRD) negativity in Cycle 2 was similar between groups (77.6% vs 76.5%). In subgroup analysis, patients with NPM1 or IDH2 mutations had higher CR rates with AV28 vs AV14 (60.9% vs 33.3%). The most common any-grade treatment-emergent adverse events (TEAEs) were thrombocytopenia (61.5%), neutropenia (60.4%), anemia (56.2%), and leukopenia (55%). Rates of Grade ≥3 adverse events (AEs), serious adverse events (SAEs), and early mortality were similar between treatment groups.

Key learning: AV14 failed to demonstrate non-inferiority to AV28 for CR in older, intensive chemotherapy-ineligible patients with unselected ND AML. Further investigation is required to determine the optimal dosing regimen of azacitidine + venetoclax in different genetic subsets.