Dr. Sehgal on Key Targetable Alterations in AML

Alison R. Sehgal, MD, assistant professor of medicine, hematologist/medical oncologist, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, discusses key targetable alterations in acute myeloid leukemia (AML).

IDH1/2 mutations are important targetable alterations in AML​. Moreover, the targeted therapies ivosidenib (Tibsovo), an IDH1 inhibitor and enasidenib (Idhifa), an IDH2 inhibitor ​are approved for use in patients with AML. Further evaluation of these therapies ​is planned to determine whether combination strategies could be more beneficial to patients, Sehgal says.

Additionally, gilteritinib (Xospata), a FLT3 inhibitor​, received regulatory approval in Novembe​r 2018 for ​the treatment of adult patients with relapsed/refractory AML, who harbor FLT3 mutations, as detected by an FDA-approved test. Like ivosidenib and enasidenib, gilteritinib is undergoing further testing to determine if it is more effective when used in combination ​regimens. ​Additionally, data are emerging regarding the role of gilteritinib in the pre- and post-transplant settings ​for patients with AML, Sehgal adds.

Notably, the lack of agents that target TP53 represents an unmet need in the AML space; however, ongoing research efforts are evaluating different therapies that may yield a survival advantage in patients who harbor TP53 mutations, Sehgal concludes.