Quizartinib Combinations Under Study in FLT3-ITD–Mutated AML
Posted: Friday, May 21, 2021
The combination of the FLT3 inhibitor quizartinib plus the hypomethylating agent azacitidine appears to effectively treat patients with FLT3-internal tandem duplication (ITD)–mutated acute myeloid leukemia (AML), a disease with a generally poor prognosis. Hagop M. Kantarjian, MD, of The University of Texas MD Anderson Cancer Center, and colleagues reported in Haematologica that, additionally, combination treatments of quizartinib plus either azacitidine or low-dose cytarabine are well tolerated, with just two patients experiencing grade 3 QTc prolongation.
The researchers’ open-label phase I/II trial involved 73 patients, all but 3 with this particular subtype of AML. A total of 34 patients, required by the trial design to 60 years of age or older, received a quizartinib-based regimen as first-line treatment for FLT3-ITD–mutated AML or myelodysplastic syndrome; 39 patients (aged 58 to 80), 36 of whom had FLT3-ITD–mutated disease, received the drugs as first-salvage treatment of AML.
In patients receiving first-line treatment, composite responses were generated in 87% of patients (13 of 15; eight complete responses) treated with quizartinib/azacitidine. The median overall survival for the 15 patients was 19.2 months. For the comparable group treated with quizartinib/low-dose cytarabine, 74% experienced a composite response (14 of 19; one complete response), and the median overall survival for the 19 patients was 8.5 months.
Among previously treated patients, 64% of the quizartinib/azacitidine cohort achieved a composite response (16 of 25); the composite response rate was 29% (4 of 14) in the quizartinib/low-dose cytarabine group. Here, the median overall survival for patients treated in the azacitidine and low-dose cytarabine cohorts was 12.8 versus 4 months, respectively. None of the three patients with FLT3-wild type disease responded to quizartinib-based therapy.
The investigators concluded that prospective randomized trials should be conducted to determine whether the combination “might improve the probability of response and the response duration in these patients.”
Disclosure: The study authors reported no conflicts of interest.