In an analysis from the phase III VIALE-A study reported in the Journal of Clinical Oncology, Keith W. Pratz, MD, and colleagues found that among treatment-naive patients with acute myeloid leukemia (AML) who experienced complete remission after receiving treatment with venetoclax/azacitidine, those who achieved measurable residual disease (MRD)-negative (10−3) status had an improved prognosis vs those who did not.
As stated by the investigators, “There is limited evidence on the clinical utility of monitoring MRD in patients with AML treated with lower-intensity therapy. Herein, we explored the outcomes of patients treated with venetoclax and azacitidine who achieved composite complete remission and MRD < 10−3 in the VIALE-A trial.”
Study Details
In VIALE-A, patients were randomly assigned to receive venetoclax and azacitidine or placebo and azacitidine. The current analysis includes patients in the venetoclax/azacitidine group who achieved composite complete remission (complete remission or complete remission with incomplete hematologic recovery). Outcomes were assessed according to whether patients did or did not achieve MRD-negative response, defined as < 1 residual blast per 1,000 leukocytes (10−3).
Key Findings
Among 286 patients assigned to venetoclax/azacitidine, 190 achieved composite complete remission; of these, 164 (86%) were evaluable for MRD. Among the 164 patients, MRD-negative response was achieved in 67 (41%), with 97 (59%) having MRD ≥ 10−3.
Patients who achieved composite complete remission and MRD < 10^−3 with venetoclax and azacitidine had longer duration of remission, event-free survival, and overall survival than responding patients with MRD ≥ 10^−3.— Keith W. Pratz, MD, and colleagues
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Median follow-up was 22.1 months (range = 1.3–30.1 months) among patients with MRD-negative response and 20.8 months (range = 2.3–30.7 months) among those without MRD-negative response.
Among patients with vs without MRD-negative response: median duration of remission was not reached vs 9.7 months (hazard ratio [HR] = 0.37, 95% confidence interval [CI] = 0.22–0.61); median event-free survival was not reached vs 10.6 months (HR = 0.35, 95% CI = 0.22–0.56); and median overall survival was not reached vs 18.7 months (HR = 0.30, 95% CI = 0.17–0.53). Estimated 12-month rates for duration of remission, event-free survival, and overall survival were 81.2% vs 46.6%, 83.2% vs 45.4%, and 94.0% vs 67.9%, respectively.
In overall survival multivariate analysis, composite complete remission with MRD < 10−3 was significantly associated with improved survival (adjusted HR = 0.285, 95% CI = 0.159–0.510, P < .001).
The investigators concluded, “Patients who achieved composite complete remission and MRD < 10−3 with venetoclax and azacitidine had longer duration of remission, event-free survival, and overall survival than responding patients with MRD ≥ 10−3.”
Dr. Pratz, of the Abramson Cancer Center, Perelman Center for Advanced Medicine, University of Pennsylvania, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
