Venetoclax with Decitabine Versus Decitabine Monotherapy in Elderly Acute Myeloid Leukemia: A Propensity Score Matched Analysis

Given the synergistic activity of venetoclax (VEN) in combination with a hypomethylating agent (HMA) in preclinical models of acute myeloid leukemia (AML), HMA+VEN therapy had been tried for AML patients unfit for intensive chemotherapy. Then, the US Food and Drug Administration approved VEN in combination with azacitidine (AZA) or decitabine (DEC) based on a phase 3 study of VIALE-A. Of note, the VIALE-A trial only compared AZA+VEN with AZA monotherapy and no data were comparing 5 days of DEC+VEN with DEC monotherapy. Thus, we compared newly diagnosed older adults with AML who received DEC+VEN with those treated with DEC monotherapy.

We retrospectively reviewed the data from February 2013 to December 2021, of newly diagnosed AML patients aged 65 years or older who received 5 days of DEC (N=230) or DEC combined with 400mg of VEN (N=73). To relieve the bias, we constructed the propensity score matched cohort calculating propensity score by logistic regression model using established prognostic pretreatment factors. We compared overall survival (OS), and treatment response between the two groups.

In the propensity-score matched cohort, the median age of all patients was 71 years (Interquartile range: 68-76), and the median follow-up period was 15.4 months (9.4-21.6). Baseline characteristics of both groups were similar except for the rate of proceeding with allogeneic hematopoietic stem cell transplantation (allo-HSCT); Only 5.4% (N=4) of the DEC group underwent allo-HSCT, whereas, in the DEC+VEN group, 25.7% (N=19) of the patients received allo-HSCT (p<0.01). Majority of those patients underwent allo-HSCT in a leukemia-free state (complete remission, complete remission with incomplete hematologic recovery, and morphologic leukemia-free state) with an exception of two patients in the DEC+VEN group.

The median OS of the DEC+VEN group was 13.4 months (95% confidence interval: 8.7-Not achieved [NA]), which was superior to that of the DEC group (8.3 months [5.0-10.5]), p<0.01, Figure A). OS censored at the time of HSCT showed 15.3 months (8.6-NA) versus 8.2 months (5.0-10.3), respectively (p<0.01). In the best response, 70.3% of the patients obtained a leukemia-free state after DEC+VEN treatment, compared with 24.3% of the DEC treatment group (p<0.01) (Figure B). In particular, patients in the DEC+VEN group who underwent allo-HSCT in leukemia-free state showed favorable survival after allo-HSCT (median OS from allo-HSCT: not reached [8.9-NA]).

In conclusion, DEC+VEN showed better treatment response than DEC monotherapy in older adults with newly diagnosed AML, resulting in superior OS compared to DEC monotherapy. Considerable patients in the DEC+VEN group became fit for allo-HSCT and had favorable survival outcomes. These real-world data can help in choosing HMA for combination with VEN in these elderly population. Furthermore, our data support the necessity of comparison of randomized trials of HMA+VEN vs intensive chemotherapy.

No relevant conflicts of interest to declare.