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Azacitidine maintenance in AML post induction and posttransplant

期刊

CURRENT OPINION IN HEMATOLOGY
卷 29, 期 2, 页码 84-91

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOH.0000000000000700

关键词

acute myeloid leukemia; azacitidine; maintenance therapy; transplant

资金

  1. Bristol-Myers Squib

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Disease relapse is the leading cause of death for patients with acute myeloid leukemia (AML). Recent studies have shown that oral azacitidine analogue CC-486, used as postremission therapy, can improve overall survival and have a positive impact on disease-free survival when used as maintenance therapy post allo-HCT. However, conflicting results from different trials highlight the need for robust study designs to identify patients who will benefit the most from this treatment approach.
Purpose of review Disease relapse remains the most common cause of death among patients with acute myeloid leukemia (AML) following induction therapy and allogeneic hematopoietic cell transplant (allo-HCT). Prolonging the duration of remission with minimal nonrelapse mortality risk is an area of unmet need for AML patients. Recent findings In QUAZAR AML-001 study, the oral azacitidine analogue CC-486 demonstrated an overall survival (OS) benefit when given as postremission therapy (PRT) for patients in CR1 that were ineligible to proceed to allo-HCT. Used as maintenance post allo-HCT, CC-486 has also shown safety with encouraging disease-free survival (DFS). Although a recent randomized trial of parenteral azacitidine vs. placebo post allo-HCT failed to show relapse reduction, a subsequent meta-analysis of maintenance studies posttransplant has shown good utility with this approach. Such conflicting results emphasize the need for robust study designs to identify subsets of patients that derive maximal benefits using latest tools to risk stratify relapse risk. PRT with hypomethylating agents is feasible and in select population, there is a survival advantage with CC-486. Better understanding of distinct epigenetic and immunomodulatory properties of azacitidine, holds significant promise to synergize pharmacologic and cellular drivers of disease control as PRT in future AML trials.

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