Dr Borate on Efficacy Data for Shorter Venetoclax-Plus-Azacitidine Dosing in AML

“There’s a subset of patients with AML who are older who might be fine with [receiving] less than 28 days [of venetoclax] for 2 cycles, but our study was not powered to look at specific subsets.”

Uma Borate, MBBS, MS, a physician and professor of hematology in the Department of Internal Medicine at The Ohio State University Comprehensive Cancer Center—James, discussed results from the phase 2 OPTI-AML trial, a substudy of the phase 1b/2 Beat AML trial (NCT03013998).

OPTI-AML compared 14-day vs 28-day dosing schedules of venetoclax (Venclexta) combined with with azacitidine (Vidaza) in patients 60 years and older with newly diagnosed acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy. The trial missed its primary end point of complete response (CR) within the first 2 cycles, with patients achieving a CR rate of 49.4% (95% CI, 38.2%-60.6%) with the 28-day schedule vs 43.0% (95% CI, 32.4%-54.2%) with the 14-day schedule.

Contrary to the hypothesis that a shorter venetoclax course would reduce rates of toxicity, cytopenias, hospital stays, and early deaths, these outcomes did not differ between the arms, Borate began, noting that similar proportions of patients receiving both schedules developed low blood counts requiring hospitalization, and count recovery occurred at a similar rate in each arm.

The CR rate difference between the arms, although numerically favoring the 28-day arm, was not statistically significant, she added, making it hard to conclude that one schedule outperformed the other. Among patients with NPM1 or IDH2 mutations, CR rates were higher in the 28-day arm than the 14-day arm, she said, cautioning that each arm included only approximately 10 patients with NPM1-mutated disease and that the trial was not powered for subgroup analysis.

Excluding these mutations, the CR rates were similar in both arms, according to Borate. Undertreating patients with NPM1-mutated AML should be avoided, as these patients tend to respond well to therapy, she explained. However, she emphasized that the AML field needs to define appropriate levels of venetoclax exposure by genomic subgroup. An older subset of patients with AML may achieve responses with fewer than 28 days of venetoclax for 2 cycles, Borate said, although this all-comers trial was not powered to define efficacy in that subset, pointing to a need for larger, subgroup-focused studies.