Eunice Wang, MD, Chief of Leukemia at Roswell Park Comprehensive Cancer Center, and colleagues presented the long-term results of a phase II clinical trial combining crenolanib, a second-generation FLT3 inhibitor, with standard intensive chemotherapy for the treatment of adults with newly diagnosed FLT3-mutant acute myeloid leukemia (AML) at the 2022 ASCO Annual Meeting (Abstract 7007).
Eunice Wang, MD
In this multicenter clinical trial, 44 patients with newly diagnosed FLT3-mutant AML received standard front-line induction chemotherapy with cytarabine for 7 days and daunorubicin or idarubicin for 3 days. Starting on day 9, crenolanib, which is an active inhibitor of FLT3- ITD, TKD, and variant AML mutations, was administered three times per day until 3 days before the next chemotherapy treatment. Most patients (75%) had FLT3-ITD mutations, eight patients (18%) had TKD mutations, and three patients (7%) had both ITD and TKD mutations.
After one treatment cycle, 73% of patients experienced clinical responses, and 86% of patients responded to treatment after two cycles. Better responses were noted in younger patients (≤ 60 years) and those with FLT3-ITD mutations.
The most common treatment-related adverse events were diarrhea, nausea, and febrile neutropenia, and six patients required crenolanib dose reduction during treatment. Approximately 15% of patients experienced disease relapse, but mutational analysis in these patients showed clearance of multiple FLT3 mutations and no new FLT3 clones.
“Our results were highly promising, with more than 80% of patients who received the crenolanib chemotherapy combination achieving clinical responses after treatment, and more than half still alive after almost 4 years,” said Dr. Wang, principal investigator of the clinical trial and senior author of the study. “We believe that addition of this next-generation FLT3 inhibitor to conventional chemotherapy could significantly improve outcomes and become the new standard of care for patients with FLT3-mutant AML.”
A larger, phase III clinical trial (ClinicalTrials.gov identifier: NCT03258931) randomly assigning patients with newly diagnosed FLT3-mutant AML to receive either crenolanib or midostaurin is underway at 31 sites and currently enrolling patients.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
