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Quizartinib-Based Combos Improve Outcomes in AML, MDS
Phase 1/2 study findings demonstrate the clinical efficacy of quizartinib plus azacitidine or low-dose cytarabine for the treatment of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS; Haematologica. 2021 Aug 1;106(8):2121-2130.)
According to lead investigator Mahesh Swaminathan, MD, Department of Leukemia, University of Texas MD Anderson Cancer Center, and colleagues, FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation in AML is typically associated with poor prognosis.
Thus, Dr Swaminathan et al aimed to determine whether the combination of quizartinib, a selective and potent FLT3 inhibitor, with azacitidine or low-dose cytarabine improved outcomes in patients with FLT3-ITD-mutated AML or MDS.
The open-label, phase 1/2 trial, enrolled 73 patients (34 frontline, 39 first-salvage) who had first-salvage treatment for FLT3-ITD AML, or were age <60 years with untreated MDS or AML, to receive quizartinib plus azacitidine or low-dose cytarabine.
Among previously untreated patients, a composite response (CRc) was achieved in 13 out of 15 (87%) in the quizartinib plus azacitidine arm, and 14 out of 19 (74%) in the quizartinib plus low-dose cytarabine arm. The median overall survival (OS) for patients receiving quizartinib plus azacitidine was 19.2 months and patients receiving quizartinib plus low-dose cytarabine was 8.5 months. Recurrence free survival (RFS) rates were 10.5 and 6.4 months, respectively.
Among previously treated patients, 16 (64%) from the quizartinib plus azacitidine arm and 4 (29%) from the quizartinib plus low-dose cytarabine arm achieved CRc. The median OS was 12.8 versus 4 months, respectively.
QTc prolongation of grade 3 occurred in only 1 patient per cohort.
“Quizartinib-based combinations, particularly with AZA, appear effective in both frontline and first-salvage for patients with FLT3-ITD-mutated AML and are well tolerated,” concluded Dr Swaminathan.—Emily Bader
