FDA Approves Four Novel Therapies for Acute Myeloid Leukemia 

A report published in 2018 in The Hemotologist mentions the fact that most of the therapies introduced over the years for acute myeloid leukemia (AML) simply meant optimizing the use of older drugs.

For example, the use of high-dose cytarabine for consolidation (follow-up) therapy or an increased dose of daunorubicin for induction (initial) therapy. This was in spite of the fact that researchers had improved their knowledge of the origination and development of AML over the past ten years.

AML is the most common form of leukemia in the United States in terms of the number of people newly diagnosed. It represents a major area of unmet need. Although the five-year survival rates have improved since 1975, they remain on average between 25 to 29 percent.

Four Novel Therapies

However, the good news is that in the last few years there has been major progress in AML. The FDA has approved four novel drug therapies to treat various subtypes of the disease that have the most adverse outcomes.

Of the four new therapies

  • two are FDA approved for patients with specific genetic abnormalities
  • one deals with myelodysplasia-related changes (AML-MRC) and
  • the fourth is the first FDA approved drug for therapy-related AML (t-AML).

The mutations FLT3 and IDH2 that are affected by the newly-approved drugs are also found in myelodysplastic syndromes and other myeloid leukemias related to AML. This creates anticipation that the therapies will lead to further progress in the treatment of patients with AML.

The following represents a brief description of the four newly-approved drugs.

Midostaurin for FLT3-mutant AML

Midostaurin, a small-molecule kinase inhibitor, is the first drug for AML to be approved by the FDA since the year 2000.

Midostaurin was approved in combination with cytarabine and daunorubicin induction together with cytarabine consolidation. Almost one-third of AML patients bear the FLT3 mutation which is known to be an adverse prognosticator.

Over 3000 patients were screened for the study but only 717 patients were randomized for treatment. The approval of the first FLT3 inhibitor gives hope for additional FLT3 inhibitors in future AML clinical trials. Additional information about Midostaurin may be found here.

Enasidenib for relapsed or refractory AML

The FDA granted regular approval to enasidenib for the treatment of relapsed or refractory (a condition which does not respond to treatment) AML with an isocitrate dehydrogenase-2 (IDH2) mutation. RealTime IDH2 Assay, a companion diagnostic that detects the IDH2 mutation, was approved concurrently.

The FDA approval is the first for relapsed or refractory AML specifically with an IDH2 mutation. The approval was based on Study AG221-C-001 and included 199 adults with the IDH2 mutation as detected by the RealTime IDH2 Assay. For more information please refer to clinical trial NCT01915498 or visit this site.

 CPX-351 (Vyxeos) for newly diagnosed t-AML or AML-MRC

Vyxeos, a liposomal formulation, releases a set amount of cytarabine and daunorubicin throughout the body. The drugs are enclosed in a liposome which is a coating or lipid sphere. This is an improvement in delivery as well as the amount of time the drugs remain within the patient’s system.

Vyxeos, the first FDA approved therapy specifically for high-risk AML patients, was approved based on the results of a phase III clinical trial that tested CPX-351. The goal of the trial was to evaluate the efficacy and safety of CPX-351 as compared to the standard cytarabine and daunorubicin induction. The study involved 309 patients ages 60 to 75 with newly diagnosed AML-MRC5 or t-AML.

The dose, which is administered as an infusion into the vein, is determined by the physician based upon the patient’s weight, height, and general health. Liposomal therapy is known to deliver high concentrations of the drugs to the diseased target. The liposome carrier plays a role in reducing the harmful effects of certain drugs on healthy tissues.

More information about Vyxeos may be found here.

Gemtuzumab ozogamicin (GO) 

GO (Mylotarg) was approved in 2000 for AML but then it was removed in 2010 for failure to confirm efficacy data and also due to safety concerns.

The drug was returned to the market in 2017 after FDA approval at a lower dose and schedule. It is now also targeted to a different patient population.

GO has been FDA approved as follows:

  • Gemtuzumab ozogamicin for newly diagnosed CD33-positive AML in adults
  • Gemtuzumab ozogamicin for relapsed/refractory CD33-positive AML in adults and
  • Gemtuzumab ozogamicin for pediatric patients who are at least two years of age.

GO in Combination: GO’s approval in combination with chemotherapy was based on the ALFA-0701 study. This Phase III study involved 271 patients with newly diagnosed AML who were between 50 to 70 years of age. (NCT00927498)

GO as a Single Agent: The approval of GO as a single agent was based on two additional clinical trials.

  • AML-19 which is a phase III study that compares GO to the best supportive care and
  • MyloFrance-1 which is a phase II that studies AML patients in the first relapse.

Additional information can be found here.


Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia four years ago. He was treated with a methylating agent While he was being treated with a hypomethylating agent, Rose researched investigational drugs being developed to treat relapsed/refractory AML.

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