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

February 2018, Vol 9, No 1 | Payers' Perspectives In Oncology: ASH 2017 Highlights

Atlanta, GA—Although there have been major advancements in the treatment of hematologic malignancies in recent years, according to Richard Pazdur, MD, Director, FDA’s Oncology Center of Excellence, 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 (50 mg orally twice daily on days 8-21 of each cycle) 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, a nucleoside metabolic inhibitor, and daunorubicin, an anthracycline topoisomerase inhibitor, 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.

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 patients were randomized to gemtuzumab ozogamicin plus daunoru­bicin and cytarabine, or to daunorubicin and cytarabine without gemtuzu­mab ozogamicin. 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 of disease 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.


In August 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, noting 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 with an IDH2 mutation as detected by the aforementioned assay. Patients received enasidenib (100 mg orally daily), and after a median follow-up of 6.6 months, 23% had a complete response (CR) or a CR with partial hematologic recovery (CRh) lasting a median of 8.2 months. A total of 19% of patients had a median CR of 8.2 months, and 4% had a median CRh 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. Of the 42 patients who did not require transfusions at the start of the trial, 76% maintained transfusion independence.

“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.”

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