On Tuesday, June 7, Eunice Wang, MD, Chief of Leukemia at Roswell Park Comprehensive Cancer Center, will present the long-term results of a phase 2 clinical trial combining crenolanib, a second-generation FLT3 inhibitor, with standard intensive chemotherapy for treatment of adults with newly diagnosed FLT3-mutant acute myeloid leukemia (AML). Dr. Wang will discuss the findings at the American Society of Clinical Oncology (ASCO) annual meeting 2022, at 11:57 a.m. CDT, in Hall S, room 100a, during the Hematologic Malignancies-; Leukemia, Myelodysplastic Syndromes, and Allotransplant oral abstract session (abstract 7007).
In this multicenter Roswell Park-led 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, 8 patients (18%) had TKD mutations, and 3 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.
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. 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."
Dr. Wang, principal investigator of the clinical trial and senior author of the study
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.
A larger, phase 3 clinical trial (NCT03258931) randomizing patients with newly diagnosed FLT3-mutant AML to receive either crenolanib or midostaurin is underway at 31 sites and currently enrolling patients at Roswell Park.