Venetoclax Plus Azacitidine Shows Encouraging Results in FLT3-Mutated AML

By Leah Sherwood - Last Updated: March 29, 2023

When treated with the combination of venetoclax plus azacitidine, treatment-naïve acute myeloid leukemia (AML) patients with FLT3 mutations and those with FLT3 wild-type had similar outcomes, according to a recent study.

The results were published in Clinical Cancer Research in an article by Marina Konopleva, MD, PhD, of The University of Texas MD Anderson Cancer Center, and colleagues.

The investigators pooled data from patients enrolled in a phase III study that compared patients treated with venetoclax plus azacitidine or placebo plus azacitidine, and a prior phase Ib study where patients were treated with venetoclax plus azacitidine. Enrolled patients were ineligible for intensive therapy due to age (75 years or older) or comorbidities.

Patients on venetoclax plus azacitidine received venetoclax 400 mg orally (days 1-28) and azacitidine 75 mg/m2 on days 1-7 of a 28-day cycle.

The FLT3 mutation was analyzed centrally on pretreatment bone marrow aspirates. In the biomarker evaluable population, the mutation was detected in 42 (15%) patients in the venetoclax plus azacitidine cohort and 22 (19%) patients in the placebo plus azacitidine group.

The results for FLT3-mutated and FLT3 wild-type patients on the two treatments are shown in TABLE 1. Composite complete remission (CRc) is defined as complete remission (CR) plus CR with incomplete hematologic recovery. The table also shows the median duration of remission (DoR) and median overall survival (OS).

TABLE 1. Results for FLT3-Mutated and FLT3 Wild-Type Patients

Venetoclax plus azacitidine Placebo plus azacitidine
CRc 67% 36%
DoR (months) 17.3 5.0
Median OS (months) 12.5 8.6
FLT3 wild-type
CRc 67% 25%
DoR (months) 18.4 13.4
Median OS (months) 14.7 10.1

Within the FLT3-mutated patients treated with venetoclax plus azacitidine, comparing the FLT3-ITD versus FLT3-TKD populations, the CRc was 63% versus 77%, respectively, and median OS was 9.9 versus 19.2 months. In co-mutated FLT3-ITD plus NPM1 patients, CRc was 70%, median DoR was not reached, and median OS was 9.1 months.

There were no unexpected toxicities in the venetoclax plus azacitidine group, according to the investigators.


Konopleva M, Thirman MJ, Pratz KW, et al. Impact of FLT3 mutation on outcomes after venetoclax and azacitidine for patients with treatment-naïve acute myeloid leukemia. Clin Cancer Res. 2022;28(13):2744-2752. doi:10.1158/1078-0432.CCR-21-3405

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