In just over a year, the treatment of acute myelogenous leukemia (AML) in adult patients has undergone something of a revolution. Since mid-2017, the U.S. Food and Drug Administration has approved nine new targeted therapies for the disease, in contrast to none during the previous 12 years.
The approvals amount to a “game-changer for how we think about treating different groups of patients with AML,” says Daniel DeAngelo, MD, PhD, chief of the Division of Leukemia at Dana-Farber. While the approvals are limited to specific subsets of patients — based on age, the genetic characteristics of the cancer, and other factors — trials are underway to determine if the drugs are also safe and effective in others with AML.
The newly approved agents include:
- Venetoclax, approved in Nov. 2018 in combination with the chemotherapy drugs azacytidine, decitabine, or low-dose cytarabine for adults with AML who are age 75 or older, or have other conditions that make them ineligible for chemotherapy. The approval was granted on an accelerated basis after the combinations generated remissions in 65 percent of such patients in a phase II clinical trial. The approval is conditional on the results of a larger, phase III trial currently under way.
- Midostaurin, approved in April 2017 for adults newly diagnosed with AML that carries a mutation in the FLT3 gene.
- Gilteritinib, approved in Nov. 2018 for adults with relapsed or refractory (resistant to other therapies) AML with a FLT3 mutation. (Another targeted drug, quizartinib, is expected to be approved in the near future for the same category of patients.)
- Glasdegib, approved in Nov. 2018 in combination with low-dose cytarabine for newly diagnosed AML in patients age 75 or older or who have co-existing conditions that preclude the use of intensive chemotherapy.
- Enasidenib, approved in August 2107 for adults with relapsed or recurrent AML with a mutation in the IDH2 gene.
- Ivosidenib, approved in July 2018 for adults with relapsed or recurrent AML with a mutation in the IDH1 gene.
- Vyxeos, approved in August 2017 for adults newly diagnosed with AML that arose as a complication of chemotherapy or radiation therapy.
- Mylotarg, approved in September 2017 for adults with newly diagnosed AML whose tumors test positive for the CD33 antigen, and for patients who have relapsed or not responded to initial treatment.
- Tagraxofusp-erzs, approved in December 2018 for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), a subtype of AML.
The collection of newly approved drugs for AML represents a flowering of years of research into the disease. Because the new agents target specific abnormal proteins, they’re approved only for patients whose leukemia cells carry those abnormalities. Patients therefore need to have their tumor tissue tested for molecular irregularities before the disease relapses in order to determine if they are eligible for any of the new therapies.