Patients with acute myeloid leukaemia (AML) who fail to respond to, or relapse after chemotherapy often have dismal outcomes. Now, data from the phase III ADMIRAL trial confirm the efficacy of the FLT3 inhibitor gilteritinib in patients with activating FLT3 mutations in this setting.
A total of 371 adult patients with FLT3-mutant AML who either failed to respond to, or had disease relapse following complete remission in response to anthracycline-based induction chemotherapy were randomized (2:1) to receive gilteritinib or investigator’s choice of salvage chemotherapy. The primary end points were overall survival (OS) and percentage of patients with complete remission and full or partial haematological recovery.
After a median follow-up duration of 17.8 months, patients in the gilteritinib group had a median OS of 9.3 months versus 5.6 months in the chemotherapy group (HR 0.64, 95% CI 0.49–0.83; P < 0.001). Furthermore, 34% of patients receiving gilteritinib had complete remission with at least partial haematological recovery versus 15.3% in the chemotherapy group (risk difference 18.6%, 95% CI 9.8–27.4), including complete haematological recovery rates of 21.1% and 10.5%, respectively.
Common treatment-related grade ≥3 adverse events among patients receiving gilteritinib included febrile neutropenia (45.9%), anaemia (40.7%), and thrombocytopenia (22.8%). Patients receiving gilteritinib were more likely to discontinue treatment owing to adverse events than those receiving chemotherapy (15% versus 7.3%) and had a similar risk of treatment-emergent adverse events leading to death (5.7% versus 7.3%). However, when adjusted for the duration of treatment exposure, patients in the gilteritinib arm had fewer adverse events than those in the chemotherapy arm (19.34 versus 42.44 events per patient-year).
These findings confirm the superior efficacy of gilteritinib versus chemotherapy for patients with FLT3-mutant AML.
Perl, A. E. et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N. Engl. J. Med. 381, 1728–1740 (2019)
About this article
Cite this article
Sidaway, P. Gilteritinib improves outcomes in AML. Nat Rev Clin Oncol 17, 69 (2020). https://doi.org/10.1038/s41571-019-0305-2