The FDA approved ivosidenib for patients with IDH1-mutant relapsed/refractory acute myeloid leukemia. The approval was based on results of a phase I trial in which 32.8% of patients treated with the drug had a complete remission or a complete remission with a partial hematologic recovery.

The FDA recently approved the first IDH1 inhibitor—ivosidenib (Tibsovo; Agios)—for patients with relapsed/refractory IDH1-mutant acute myeloid leukemia (AML). The agency concurrently approved the RealTime IDH1 Assay (Abbott Laboratories) as a companion diagnostic.

The approval was based on results of a single-arm, phase I trial of 174 patients treated with the drug: 32.8% had a complete remission or a complete remission with a partial hematologic recovery—meaning that less than 5% of bone marrow cells were blasts—that lasted for a median of 8.2 months. Additionally, 37% of the 110 patients who required blood or platelet transfusions at the start of the study did not need one for at least 56 days after treatment. Initial results from the trial were published in The New England Journal of Medicine earlier this year.

Ross Levine, MD, of Memorial Sloan Kettering Cancer Center in New York, NY, says that he views the approval, along with that of the IDH2 inhibitor enasidenib (Idhifa; Celgene) in August 2017, as “the first step towards dramatically improved outcomes for AML.” About 20% of patients with the disease have mutations in one of the two genes.

Levine notes that until now, patients with relapsed/refractory AML and IDH1/2 alterations have had to rely on chemotherapy, which often doesn't work. “I think the idea that you have an effective, much less toxic treatment in a tough clinical scenario is really important,” he says. “It really provides a therapeutic option where one was pretty desperately needed.”

Levine hopes that IDH inhibitors can ultimately be used as a first-line therapy. Ongoing trials are testing the drugs alone and in combination with chemotherapy in newly diagnosed patients. Also, enasidenib and other drugs are being tested in the Beat AML Master trial, co-led by Levine, which is using genomic information to match patients to targeted therapies.

“Molecular analysis of leukemia patients is hopefully going to allow us to finally come up with a therapeutic approach that is as patient specific as are the genetics and epigenetics of the disease,” he says. –Catherine Caruso

©2018 American Association for Cancer Research.
2018
American Association for Cancer Research.