Decitabine Plus Venetoclax Outperforms Intensive Chemotherapy Across Risk Groups

For older and unfit patients with acute myeloid leukemia (AML), venetoclax plus hypomethylating agents (HMAs) have been established as a standard of care and have demonstrated improved survival compared with HMAs alone, but it is unknown how this approach compares with intensive chemotherapy in “fitter” patients. In results from a study presented at EHA25 Virtual, the 25th European Hematology Association Congress, researchers suggested that venetoclax plus decitabine improves outcomes compared with intensive chemotherapy, particularly in patients considered at high risk for treatment-related mortality.

“There is lack of consensus regarding objective methods of determining fitness for chemotherapy, and in the clinic, this assessment is often subjective,” explained study author Abhishek Maiti, MD, from MD Anderson Cancer Center in Houston, during his presentation. “Hence, questions have been raised regarding whether all patients on [prior] venetoclax trials were truly unfit or not. If they were not unfit, could they have benefited more from intensive chemotherapy instead?”

In this analysis, researchers compared outcomes of older patients with AML enrolled in a phase II trial of DEC10-VEN (decitabine 20 mg/m2 for 10 days every 4-8 weeks plus venetoclax daily on days 1-28 of cycle 1 and days 1-21 of subsequent cycles) with outcomes from a matched historical cohort of patients treated with intensive chemotherapy that included cytarabine ≥1 g/m2.

Patients were stratified for “fitness” according to a validated treatment-related mortality risk score (high risk was defined as a score >13.1).

Dr. Maiti reported results from 85 patients who received DEC10-VEN and 170 who received intensive chemotherapy. In both cohorts, 28% of patients were considered at high risk for treatment-related mortality (n=24 and 48, respectively).

Over a median follow-up of 16 months in the DEC10-VEN group and 55 months in the chemotherapy group, treatment with the HMA and venetoclax combination was associated with improvements in complete response rates, treatment-related mortality, and survival in patients considered “unfit.”

In patients at low risk of treatment-related mortality, treatment with DEC10-VEN was associated with higher complete response rates (OR=2.50; 95% CI 1.08-5.74; p=0.03) and lower rates of 60-day mortality (OR=0.22; 95% CI 0.05-1.00; p=0.05) compared with intensive chemotherapy, but the differences in 30-day mortality and overall survival were not statistically significant.

Dr. Maiti added that overall survival with DEC10-VEN was longer than with intensive chemotherapy in most subgroups analyzed, including in mutational subgroups.

The researchers concluded that DEC10-VEN appears to benefit patients with newly diagnosed AML who have a high or low risk of treatment-related mortality. “Although propensity-score matching can balance important factors, there is always the possibility of unmeasured confounders that can influence the differences observed,” Dr. Maiti said, noting a potential limitation of this study.

Study authors report relationships with AbbVie, the manufacturer of venetoclax.


Maiti A, DiNardo CD, Ravandi F, et al. 10-Day decitabine and venetoclax (DEC10-VEN) vs. intensive chemotherapy (IC) in acute myeloid leukemia (AML): a propensity score matched analysis stratified by risk of treatment-related mortality. Abstract S141. Presented as part of EHA25 Virtual; July 12, 2020.