Quizartinib a promising treatment option for FLT3-ITD-positive relapsed, refractory AML
The FMS-like tyrosine kinase 3 (FLT3) inhibitor quizartinib appears to be highly active in patients with relapsed and/or refractory acute myeloid leukaemia (AML) positive for FLT3-ITD mutation, according to the results of a phase II trial.
A total of 333 patients received the study drug once daily as an oral solution, among whom 157 were aged ≥60 years with relapsed or refractory AML within 1 year after first-line therapy (cohort 1) while the remaining 176 were aged ≥18 years with relapsed or refractory disease following salvage chemotherapy or haemopoietic stem cell transplantation (cohort 2). Doses were given at 135 mg/day for men and 90 mg/day for women.
The coprimary endpoints were the proportion of patients who achieved a composite complete remission (defined as complete remission plus complete remission with incomplete platelet recovery plus complete remission with incomplete haematological recovery) and the proportion of those who achieved a complete remission.
In cohort 1, 63 of 112 (56 percent) FLT3-ITD-positive patients and 16 of 44 (36 percent) FLT3-ITD-negative patients achieved composite complete remission, while three (3 percent) and two (5 percent) achieved complete remission, respectively. In cohort 2, 62 of 136 (46 percent) FLT3-ITD-positive patients and 12 of 40 (30 percent) FLT3-ITD-negative patients achieved composite complete remission, with five (4 percent) and one (3 percent) achieving complete remission, respectively.
In the entire cohort, commonly reported grade 3 or worse treatment-related adverse events (AEs) included febrile neutropoenia (23 percent), anaemia (23 percent), thrombocytopaenia (12 percent) and corrected QT interval prolongation (10 percent), among others. Notable serious AEs observed in <5 percent of patients were torsades de pointes (<1 percent) and hepatic failure (1 percent). In total, 125 (38 percent) deaths were recorded within the study period, with 18 cases (5 percent) due to an AE considered by the investigator to be treatment-related.
The present data indicate that targeting the FLT3-ITD driver mutation with a highly potent and selective FLT3 inhibitor is an attractive clinical strategy to help improve outcomes in AML patients with very few options, researchers said. Phase III studies will investigate quizartinib at lower starting doses.