Year: 2021
Type: article
Abstract: I n 2021, most, if not all, presentations and publications about the treatment of acute myeloid leukemia (AML) start biblically: hematologists spent 40 years in the desert of "7+3" and in 2017 reached a promised land flowing with Food and Drug Administration approvals.One of the first approvals addressed the vexing problem of FLT3mutant AML.While the FLT3-internal tandem duplication (ITD) was discovered over 25 years ago, the success of randomized clinical studies targeting the mutant FLT-3 protein only occurred years later with the RATIFY trial. 1 In this trial, the combination of the multikinase inhibitor midostaurin with induction chemotherapy led to a statistically significant improvement in the 4-year overall survival of patients with newly diagnosed FLT3-mutant AML. 2 The approval of single-agent gilteritinib, a second-generation FLT-3 inhibitor for patients with relapsed and refractory AML, based on the randomized phase III ADMIRAL trial, consolidated the role of FLT-3 inhibitors in the treatment of patients with AML. 3 But while gilteritinib was being approved, a second FLT-3 inhibitor, quizartinib, was axed by the Oncologic Drugs Advisory Committee (ODAC).Quizartinib, a potent inhibitor of FLT3-ITD but not FLT3-tyrosine kinase domain (TKD) mutations, was studied in a randomized phase III trial, for relapsed and refractory AML.Despite demonstrating a statistically significant overall survival benefit in the company-sponsored analysis of the clinical trial, concerns about dropouts in the standard treatment arm led to a negative vote against quizartinib at an ODAC meeting.Despite this, quizartinib was approved in Japan and is now a standard-of-care therapy in that country.Building on previous work showing the relative benefit of treating patients with the combination of sorafenib, a weak FLT-3 inhibitor, with azacitidine, in this issue of Haematologica, Swaminathan and colleagues 4 report the outcomes of patients with either newly diagnosed or relapsed FLT3-ITD AML treated with the combination of azacitidine or low-dose cytarabine with quizartinib.Perhaps the most impressive outcome in this trial is the high rate of composite complete response of 87% with quizartinib/azacitidine and 74% with quizartinib/lowdose cytarabine.These rates of remission are certainly
Source: Haematologica
Author: Eytan M. Stein
Institution: Memorial Sloan Kettering Cancer Center
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,157
OpenAlex ID: W3156479986