Real-World Study Shows Improved Survival with Venetoclax and HMA Combo in IDH-Mutated AML

Among patients with newly diagnosed acute myeloid leukemia (AML), receipt of venetoclax plus hypomethylating agents (HMAs) resulted in significantly higher rates of responses than patients who received non-venetoclax-containing regimens. This treatment benefit was also observed in patients unfit for intensive chemotherapy and those with IDH1/2 mutations. The results of the AML Real World Evidence Initiative were presented at the 2022 American Society of Hematology Annual Meeting.

Researchers conducted a multicenter chart review and randomly selected patients with newly diagnosed AML treated with venetoclax since April 2016 from 14 academic sites (10 in the United States, and four in Israel) who were then matched 1:1 with controls who received non-venetoclax-containing regimens since May 2015. There were 176 patients in each cohort, and patients were matched based on age (<60 years, 60-74 years, ≥75 years) and European LeukemiaNet (ELN) risk. The venetoclax-containing cohort included 116 unfit patients.

In the venetoclax cohort, 76.1% received venetoclax plus azacitidine or venetoclax plus decitabine (23.9%). Most patients in the control group (65.3%) received high-intensity regimens. Most patients (64.8%) were classified as ELN adverse risk, and this classification increased to 67.2% in the unfit subgroup.

TP53 mutations were observed in 22.2% of venetoclax-treated patients and 13.5% of control patients, while IDH1/2 mutations occurred in 19.9% and 14.6% of patients, respectively.

Composite complete remission (CRc) occurred in 65.7% of venetoclax-treated patients and 53.5% of control patients (P<.05). CR occurred in 39.6% and 43.5%, respectively (P<.53). In the unfit subgroup, 66.1% of venetoclax-treated patients and 44.6% of the control cohort achieved CRc (P<.01), while 37.5% and 36.0%, respectively, achieved CR (P=.91).

Among those with TP53 mutations, responses were not statistically different for the overall and unfit subgroup. Among those with IDH1/2 mutations, CRc was significantly higher overall in the venetoclax versus control cohorts (87.9% vs 54.2%; P<.01), as well as in the unfit subgroup (85.7% vs 52.9%; P<.05). The duration of CRc was not statistically different between the treatment cohorts.

For those who achieved CRc and had measurable residual disease (MRD) assessments, 74.0% of venetoclax-treated patients and 66.7% of control patients were MRD-negative after treatment. Similar proportions were observed overall and for IDH1/2-mutated patients in the unfit subgroup, although this was not statistically significant.

Some patients went on to undergo hematopoietic stem cell transplantation, including 6.8% in the venetoclax cohort and 14.2% in the control group (P<.05) and 6.9% and 12.1% in the unfit subgroup, respectively (P=.26). Median OS was 15.8 and 13.9 months in the venetoclax and control cohorts, respectively (P=.20) and 17.1 and 12.4 months in the unfit subgroup (P=.30). The six-month OS rate was 74.3% and 70.1%, respectively (P=.30) and 75.6% and 66.2% in the unfit subgroup (P=.10). Among patients with ≥56 days of follow-up, 61.9% and 54.8% overall (P=0.29) and 67.0% and 51.1% in the unfit subgroup (P=.05), respectively, achieved transfusion independence.

Reference

Wolach O, Garcia JS, Desai P, et al. Comparison of patients with newly diagnosed (ND) acute myeloid leukemia (AML) treated with venetoclax and hypomethylating agents vs other therapies by TP53 and IDH1/2 mutation: results from the AML Real World Evidence (ARC) Initiative. Abstract #4954. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.