A reduced venetoclax exposure of seven days showed outcomes comparable with the standard continual venetoclax exposure in older or unfit patients with newly diagnosed acute myeloid leukemia (AML), according to a retrospective analysis.
Data from the study were presented at the European Hematology Association 2024 Hybrid Congress by Christophe Willekens, MD, of Gustave Roussy in Villejuif, France.
The reduced venetoclax cohort included 82 patients from seven French centers treated with azacitidine plus venetoclax, both for seven days. The standard venetoclax cohort included 173 patients from one US center treated with venetoclax for 21 to 28 days plus decitabine for 10 days in 59% and either decitabine for five days or azacitidine for seven days in the remaining.
Reduced Duration Venetoclax Maintains Efficacy
The authors stated the “7+7” and standard regimen cohorts had comparable baseline characteristics except for secondary AML (32% vs 18%), therapy-related AML (34% vs 22%), complex cytogenetics (22% vs 39%), FLT3-ITD mutations (13% vs 3%), and RAS mutations (9% vs 24%). They noted rates of TP53, NPM1, and IDH1/2 mutations were similar.
Overall, the rates of complete remission (CR) plus CR with incomplete count recovery were 72% with the “7+7” regimen and 71% with the standard regimen (P=.089), and the rates of strictly CR were 57% and 55%, respectively (P=.72).
The median overall survival (OS) and two-year OS rate were 11.2 months and 28%, respectively, in the “7+7” group and 10.1 months and 33%, respectively, in the standard group (P=.93). The median event-free survival (EFS) and two-year EFS rate were 6.5 months and 25%, respectively, in the “7+7” group and 7.1 months and 26%, respectively, in the standard group.
Both groups had a median of one cycle until first response; “however, 42% of responders on ‘7+7’ required more than one cycle for first response where almost all responders (99%) on [standard venetoclax plus hypomethylating agent (HMA)] had a first response after cycle one,” Dr. Willekens stated.
Likewise, the median number of cycles to best response was two in the “7+7” group versus one in the standard group (P=.02).
In cycle one, the two regimens had similar rates of neutropenic fever and red cell transfusion requirements, although fewer patients in the “7+7” group required platelet transfusions (62%) versus the standard group (77%; P=.01).
Early mortality at four weeks was comparable at 2% in “7+7” patients and 6% in standard patients (P=.24), but eight-week mortality was lower in “7+7” patients at 6% versus 17% in standard patients (P=.02).
“Acknowledging the limitations of a retrospective comparison across multiple centers, we did not observe a signal for a difference in response rates or survival between shortened courses of venetoclax to seven days versus standard venetoclax-based HMA doublets,” the authors summarized.
Reference
Willekens C, Bazinet A, Chraibi S, et al. Reduced venetoclax exposure to 7 days vs standard venetoclax exposure with hypomethylating agent in older/unfit patients with newly diagnosed acute myeloid leukemia: a retrospective comparison. Abstract #P590. Presented at the European Hematology Association 2024 Hybrid Congress. June 13-16, 2024; Madrid, Spain.