Measurable residual disease monitoring in patients with acute myeloid leukemia treated with lower-intensity therapy: Roadmap from an ELN-DAVID expert panel.

With the availability of effective targeted agents, significant changes have occurred in the management of patients with acute myeloid leukemia (AML) over the past several years, particularly for those considered unfit for intensive chemotherapy. While testing for measurable residual disease (MRD) is now routinely performed in patients treated with intensive chemotherapy to refine prognosis and, possibly, inform treatment decision-making, its value in the context of lower-intensity regimens is unclear. As such regimens have gained in popularity and can be associated with higher response rates, the need to better define the role of MRD assessment and the appropriate time points and assays used for this purpose has increased. This report outlines a roadmap for MRD testing in patients with AML treated with lower-intensity regimens. Experts from the European LeukemiaNet (ELN)-DAVID AML MRD working group reviewed all available data to propose a framework for MRD testing in future trials and clinical practice. A Delphi poll served to optimize consensus. Establishment of uniform standards for MRD assessments in lower-intensity regimens used in treating patients with AML is clinically relevant and important for optimizing testing and, ultimately, improving treatment outcomes of these patients.

Guadecitabine vs treatment choice in newly diagnosed acute myeloid leukemia: a global phase 3 randomized study.

This phase 3 study evaluated the efficacy and safety of the new hypomethylating agent guadecitabine (n = 408) vs a preselected treatment choice (TC; n = 407) of azacitidine, decitabine, or low-dose cytarabine in patients with acute myeloid leukemia unfit to receive intensive induction chemotherapy. Half of the patients (50%) had poor Eastern Cooperative Oncology Group Performance Status (2-3). The coprimary end points were complete remission (19% and 17% of patients for guadecitabine and TC, respectively [stratified P = .48]) and overall survival (median survival 7.1 and 8.5 months for guadecitabine and TC, respectively [hazard ratio, 0.97; 95% confidence interval, 0.83-1.14; stratified log-rank P = .73]). One- and 2-year survival estimates were 37% and 18% for guadecitabine and 36% and 14% for TC, respectively. A large proportion of patients (42%) received <4 cycles of treatment in both the arms. In a post hoc analysis of patients who received ≥4 treatment cycles, guadecitabine was associated with longer median survival vs TC (15.6 vs 13.0 months [hazard ratio, 0.78; 95% confidence interval, 0.64-0.96; log-rank P = .02]). There was no significant difference in the proportion of patients with grade ≥3 adverse events (AEs) between guadecitabine (92%) and TC (88%); however, grade ≥3 AEs of febrile neutropenia, neutropenia, and pneumonia were higher with guadecitabine. In conclusion, no significant difference was observed in the efficacy of guadecitabine and TC in the overall population. This trial was registered at www.clinicaltrials.gov as #NCT02348489.