Combination therapies using quizartinib with either cytarabine or azacitidine are safe and effective in both frontline and first-salvage treatment for patients with FLT3-ITD-mutated acute myeloid leukemia (AML), according to study results published in Haematologica.

Mutations in the FLT3 gene are common genetic alterations in patients with AML. Quizartinib is a type 2 inhibitor that targets the inactive conformation of the FLT3 kinase domain, making it a likely candidate to help treat patients with these mutations.

In this phase 1/2, open-label study, the primary objective was to assess the safety of quizartinib paired with either azacitidine or cytarabine, as well as to determine the dose-limiting toxicity. The researchers also assessed the efficacy of the drug combinations.

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Eligible participants included adult patients with myelodysplastic syndrome or AML with relapsed or refractory disease who had received no more than 1 prior therapy. A total of 73 patients were treated, 34 as frontline treatment and 39 as first-salvage treatment. Of these, 70 completed at least 1 cycle of study treatment. A total of 38 patients received quizartinib with azacitidine (quizartinib/AZA) and 32 received quizartinib with low-dose cytarabine (quizartinib/LDAC).

The median duration of response (time from best response to either death, disease progression, date of stem cell transplantation or last follow-up, or off treatment) was 4.2 months (range, 0.2-30) with quizartinib/AZA and 3.7 months (range, 0.2-17) with quizartinib/LDAC.

Of the patients treated with quizartinib/AZA in the frontline (n=14), 8 patients (57%) had a complete response (CR). Of the patients treated with quizartinib/LDAC in the frontline (n=18), only 1 had a CR. Of the patients with relapsed or refractory disease treated with quizartinib/AZA (n=24), 2 (8%) had a CR. Of the patients with relapsed or refractory disease treated with quizartinib/LDAC (n=14), only 1 had a CR.

Among responders, minimal residual disease (MRD) was assessed in 11 patients (85%) in the quizartinib/AZA group and 12 patients (86%) in the quizartinib/LDAC group. MRD was undetectable in 5 (45%) patients treated with quizartinib/AZA and 3 (25%) with quizartinib/LDAC.

The most common nonhematologic adverse events (AEs) for the quizartinib/AZA group included hypomagnesemia (68%), hyperbilirubinemia (63%), and hypokalemia (60%). The most common hematologic AE was thrombocytopenia (15%).

The most common nonhematologic AEs for the quizartinib/LDAC group included pneumonia (58%), febrile neutropenia (36%), and hypotension (36%). The most common hematologic AEs were leukopenia (42%) and neutropenia (42%).

In assessments for survival, the median overall survival (OS) for all patients treated in the frontline was 12.4 months. The median relapse-free survival for these patients was 8 months, and it was significantly longer for patients in the quizartinib/AZA group vs the quizartinib/LDAC group (10.5 vs 6.4 months; P =.044). Patients with relapsed/refractory AML had a median OS of 6.2 months, with a trend for longer OS for those treated with quizartinib/AZA (12.8 vs 4 months; P =.053).

“With the limitations of comparisons across studies, the [composite response] rates and the median OS observed in patients treated frontline with quizartinib/AZA in this study seem to compare favorably to what has been reported with similar combinations using other FLT3 inhibitors,” the authors concluded in their report. “Our study demonstrated that quizartinib, in combination with AZA or LDAC, can be administered safely in patients with FLT3-mutated AML, whether as initial therapy or in first salvage.”


Swaminathan M, Kantarjian HM, Levis M, et al. A phase I/II study of the combination of quizartinib with azacitidine or low-dose cytarabine for the treatment of patients with acute myeloid leukemia and myelodysplastic syndrome. Haematologica. Published online April 15, 2021. doi:10.3324/haematol.2020.263392