ASH 2018 News - Episode 4
Pinkal Desai, MD, MPH, assistant professor of medicine at Weill Cornell Medical College and assistant attending physician at the NewYork-Presbyterian Hospital, discusses advances made in the treatment of patients with acute myeloid leukemia (AML).
The field of AML gained 3 landmark FDA approvals in the past 3 months: venetoclax (Venclexta), glasdegib (Daurismo), and gilteritinib (Xospata). Venetoclax and glasdegib already hold frontline indications. Venetoclax now holds an additional indication for use in combination with hypomethylating agents (HMAs) or low-dose cytarabine for patients with newly-diagnosed AML who are over the age of 75. Glasdegib is also approved in the same indication, while gilteritinib has been approved for use in patients with relapsed/refractory FLT3-mutated AML.
Data presented at the meeting showed high response rates with the combination of venetoclax and HMAs, which exceeded historical data with HMAs. Moreover, venetoclax seems to be mutation agnostic, says Desai. About 60% of patients with TP53 mutations showed a frontline response, and over 90% of those with IDH mutations showed similar responses.
The QuANTUM-R study reflected a 48% complete response rate with quizartinib in patients with FLT3-ITD-mutated AML, which will factor into the FDA’s pending decision on its priority review designation. Under the Prescription Drug User Fee Act, the FDA is expected to reach a decision on the application by May 25, 2019.
First-in-human results with the CD33-targeted bispecific T-cell engager (BiTE) antibody construct in relapsed/refractory patients were also presented at the meeting. Cytokine release syndrome was observed, as expected, but was easily treated with steroids and tocilizumab (Actemra). Two complete remissions were seen, as well as 2 incomplete remissions. With more cohorts and higher doses, Desai predicts that more patients may go into remission.
In myelodysplastic syndromes, phase III data were reported with luspatercept, a drug that counteracts the TGF-beta ligand. About 40% of low-risk patients achieved transfusion independence for 1 year, an encouraging finding for patients who fail on an erythropoietin agent, said Desai.