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Reformulating acute myeloid leukemia: liposomal cytarabine and daunorubicin (CPX-351) as an emerging therapy for secondary AML

Authors Chen EC, Fathi AT, Brunner AM

Received 1 February 2018

Accepted for publication 8 April 2018

Published 12 June 2018 Volume 2018:11 Pages 3425—3434

DOI https://doi.org/10.2147/OTT.S141212

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 3

Editor who approved publication: Dr Samir Farghaly


Evan C Chen,1 Amir T Fathi,2 Andrew M Brunner2

1Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; 2Department of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA

Abstract: Despite increasing understanding of the pathobiology of acute myeloid leukemia (AML), outcomes remain dismal particularly for patients over the age of 60 years, a population enriched for therapy-related AML (tAML) and secondary AML (sAML). For decades, the standard of care for AML has been the combination of cytarabine and daunorubicin, typically delivered in combination as “7 + 3” induction. In 2017, a liposomal-encapsulated combination of daunorubicin and cytarabine (CPX-351, Vyxeos) was approved by the US Food and Drug Administration (FDA) for use in the treatment of newly diagnosed tAML or AML with myelodysplasia-related changes (AML-MRCs). CPX-351 was designed to deliver a fixed 5:1 molar ratio of cytarabine and daunorubicin, respectively, based on the hypothesis that ratiometric dosing may be more effective than the delivery of either drug at their maximum tolerated dose. In a Phase III trial of older patients with sAML aged 60–75 years, CPX-351 was compared to “7 + 3” and was associated with a higher overall survival, event-free survival, and higher rates of complete remission (CR) and CR with incomplete hematologic recovery (CRi). These data were the basis for the approval of this new drug for use in the treatment of AML, but questions remain regarding how to best administer this agent across AML subgroups. Future directions include evaluating dose intensification with CPX-351, combining this agent with targeted therapies, and better understanding the mechanism of improved responses in tAML and AML-MRC, two entities that are historically less responsive to cytotoxic agents. In summary, CPX-351 offers an exciting new change to the landscape of AML therapy.

Keywords: acute myeloid leukemia, AML, liposome, liposomal, Vyxeos, CPX-351, cytarabine, daunorubicin

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