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Dose intensity for induction in acute myeloid leukemia: what, when, and for whom?

Journal

HAEMATOLOGICA
Volume 106, Issue 10, Pages 2544-2554

Publisher

FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.2020.269134

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Recent advances in AML therapy have shifted towards the use of novel targeted agents alongside traditional intense chemotherapy, providing remission options for patients who may not be suitable for cytotoxic treatments. These new approaches include combination therapies with hypomethylating agents and venetoclax, as well as the addition of gemtuzumab ozogamicin and FLT3 inhibitors to induction chemotherapy for specific AML subtypes. More research is needed to improve outcomes for high-risk subgroups.
Intensive chemotherapy has been the backbone of the treatment of acute myeloid leukemia (AML) for decades. However, an increase in novel targeted agents, which has been brought about in part by a deeper understanding of the genetic makeup of AML, has led to remission-inducing regimens that do not require traditional cytotoxic agents. Combinations of a hypomethylating agent (HMA) and venetoclax have doubled the chance of remission for patients considered unfit for induction chemotherapy who would have traditionally been offered single-agent HMA. In fact, this regimen may rival the complete remission rate achieved with induction chemotherapy for certain populations such as the very elderly and those with secondary AML, but equivalency has yet to be established. Further advances include the addition of gemtuzumab ozogamicin and FLT3 inhibitors to induction chemotherapy, which improves survival for patients with core-binding factor and FLT3-mutated AML, respectively. Still, much work is needed to improve the outcomes of the highest-risk subgroups: frail patients and those with high-risk cytogenetics and/or TP53 mutations. Promisingly, the landscape of AML therapy is shifting dramatically and no longer is intensity, when feasible, always the best answer for AML.

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