FDA Approval Summary: (Daunorubicin and Cytarabine) Liposome for Injection for the Treatment of Adults with High-Risk Acute Myeloid Leukemia

Clin Cancer Res. 2019 May 1;25(9):2685-2690. doi: 10.1158/1078-0432.CCR-18-2990. Epub 2018 Dec 12.

Abstract

On August 3, 2017, the FDA granted regular approval to Vyxeos (also known as CPX-351; Jazz Pharmaceuticals), a liposomal formulation of daunorubicin and cytarabine in a fixed combination, for the treatment of adults with newly diagnosed therapy-related acute myeloid leukemia (t-AML) or acute myeloid leukemia (AML) with myelodysplasia-related changes (AML-MRC). Approval was based on data from Study CLTR0310-301, a randomized, multicenter, open-label, active-controlled trial comparing Vyxeos with a standard combination of daunorubicin and cytarabine ("7+3") in 309 patients 60-75 years of age with newly diagnosed t-AML or AML-MRC. Because of elemental copper concerns with the Vyxeos formulation, patients with Wilson disease were excluded from the study. Vyxeos demonstrated an improvement in overall survival (HR 0.69; 95% confidence interval, 0.52-0.90; P = 0.005) with an estimated median overall survival of 9.6 months compared with 5.9 months for the "7+3" control arm. The toxicity profile of Vyxeos was similar to that seen with standard "7+3" with the exception of more prolonged neutropenia and thrombocytopenia on the Vyxeos arm. Because the pharmacology of Vyxeos differs from that of other formulations of daunorubicin and cytarabine, labeling includes a warning against interchanging formulations during treatment. This is the first FDA-approved treatment specifically for patients with t-AML or AML-MRC.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cytarabine / administration & dosage
  • Daunorubicin / administration & dosage
  • Drug Approval*
  • Female
  • Follow-Up Studies
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / pathology
  • Liposomes / administration & dosage*
  • Liposomes / chemistry
  • Male
  • Middle Aged
  • Prognosis
  • Risk Factors
  • Survival Rate
  • United States
  • United States Food and Drug Administration

Substances

  • Liposomes
  • Cytarabine
  • Daunorubicin