ASH Recaps “Phenomenal” Year for Acute Myeloid Leukemia Drug Approvals

Chase Doyle

February 2018, Vol 8, No 2 - ASH 2017 Highlights

There have been major advancements in the treatment of hematologic malignancies in recent years, suggested Richard Pazdur, MD, Director, FDA’s Oncology Center of Excellence, but he noted that the number of agents approved in 2017 for acute myeloid leukemia (AML) was nothing short of “phenomenal.”

At ASH 2017, clinical reviewers from the FDA highlighted 4 major drug approvals for the treatment of patients with AML, and discussed their safety and efficacy issues.


In April 2017, midostaurin (Rydapt) was approved for the treatment of adults with newly diagnosed FLT3-positive AML in combination with standard intensive induction consolidation chemotherapy. The approval of the drug, which inhibits multiple kinases with nanomolar potency, was based on the results of the RATIFY trial, in which 717 patients with treatment-naïve FLT3 mutation–positive AML were randomized 1:1 to receive standard induction and consolidation chemotherapy in combination with midostaurin or placebo. Ashley F. Ward, MD, Medical Officer, FDA’s Division of Hematology Products, reported that RATIFY met its primary end point of overall survival (hazard ratio [HR], 0.77 favoring midostaurin).

Despite a trial design that included maintenance, the FDA determined that the study did not support an indication of maintenance therapy.


Daunorubicin plus cytarabine (Vyxeos) is a liposomal combination of cytarabine and daunorubicin, and is indicated for the treatment of adults with newly diagnosed therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC). The drug was approved in August 2017, based on data from a phase 3 clinical trial of 309 patients with t-AML or AML-MRC who received the liposome-­encapsulated combination or the 2 drugs separately.

Aviva C. Krauss, MD, Medical Officer, FDA’s Division of Hematology Products, reported that the study exclusively enrolled patients with AML who have traditionally been excluded from clinical trials as a result of their poor prognosis. With a median follow-up of 20.7 months, patients receiving the combination therapy had a median overall survival of 9.6 months compared with 5.9 months for patients receiving the 2 drugs separately.

“This drug is the first chemotherapy to demonstrate an overall survival advantage over the standard of care in a phase 3 randomized study of older adults with newly ­diagnosed therapy-related AML or AML with myelodysplasia-related changes,” said Dr Krauss.


In September 2017, the FDA approved gemtuzumab ozogamicin (Mylotarg) for the treatment of adults with newly diagnosed CD33-positive AML. The FDA also approved the drug for the treatment of patients aged ≥2 years with relapsed or refractory CD33-positive AML. Although the drug originally received accelerated approval in May 2000 as a stand-alone treatment for older patients with CD33-positive AML who relapsed, it was withdrawn from the market after subsequent trials did not verify a clinical benefit and showed safety concerns, including early death.

Kelly J. Norsworthy, MD, of the FDA reported that the most recent approval includes a lower recommended dose, a different schedule in combination with chemotherapy or alone, and a new patient population. The drug’s safety and efficacy in combination with chemotherapy were studied in 271 adults with newly diagnosed CD33-positive AML. The addition of gemtuzumab ozogamicin to the standard “7 + 3” chemotherapy improved the median event-free survival by 4.8 months (HR, 0.68).

In a separate, single-arm study, 57 patients with CD33-positive AML who had 1 relapse received a single course of gemtuzumab ozogamicin. Patients with relapsed AML who received the drug had durable remissions, and 26% of patients achieved complete remission that lasted a median of 11.6 months.


On August 1, 2017, the FDA approved enasidenib (Idhifa) for the treatment of adults with relapsed/refractory AML and an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-­approved test.

“This is the first FDA approval for relapsed or refractory AML specifically with an IDH2 mutation,” said Dr Ward, who noted that this is a rare cancer with high unmet need.

The approval of enasidenib was based on an open-label, single-arm, multicenter, clinical trial that included 199 adults with relapsed or refractory AML and IDH2 mutation. A total of 19% of patients had a median complete response of 8.2 months, and 4% had a median partial hematologic recovery of 9.6 months. Of the 157 patients who needed transfusions at the trial’s start, 34% no longer required them during at least one 56-day time period while receiving enasidenib.

“This study demonstrated compelling evidence of disease palliation,” said Dr Ward. “Although enasidenib is not curative, the short-term benefit is clinically meaningful for patients seeking quality of life.”