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
Mahesh Swaminathan,
Hagop M Kantarjian,
Mark Levis,
Veronica Guerra,
Gautam Borthakur,
Yesid Alvarado,
Courtney D DiNardo,
Tapan Kadia,
Guillermo Garcia-Manero,
Maro Ohanian,
Naval Daver,
Marina Konopleva,
Naveen Pemmaraju,
Alessandra Ferrajoli,
Michael Andreeff,
Nitin Jain,
Zeev Estrov,
Elias J Jabbour,
William G Wierda,
Sherry Pierce,
Maria Rhona Pinsoy,
Lianchun Xiao,
Farhad Ravandi,
Jorge E Cortes
Affiliations
Mahesh Swaminathan
Department of Leukemia, University of Texas MD Anderson Cancer Center
Hagop M Kantarjian
Department of Leukemia, University of Texas MD Anderson Cancer Center
Mark Levis
Department of Hematological Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Veronica Guerra
Department of Leukemia, University of Texas MD Anderson Cancer Center
Gautam Borthakur
Department of Leukemia, University of Texas MD Anderson Cancer Center
Yesid Alvarado
Department of Leukemia, University of Texas MD Anderson Cancer Center
Courtney D DiNardo
Department of Leukemia, University of Texas MD Anderson Cancer Center
Tapan Kadia
Department of Leukemia, University of Texas MD Anderson Cancer Center
Guillermo Garcia-Manero
Department of Leukemia, University of Texas MD Anderson Cancer Center
Maro Ohanian
Department of Leukemia, University of Texas MD Anderson Cancer Center
Naval Daver
Department of Leukemia, University of Texas MD Anderson Cancer Center
Marina Konopleva
Department of Leukemia, University of Texas MD Anderson Cancer Center
Naveen Pemmaraju
Department of Leukemia, University of Texas MD Anderson Cancer Center
Alessandra Ferrajoli
Department of Leukemia, University of Texas MD Anderson Cancer Center
Michael Andreeff
Department of Leukemia, University of Texas MD Anderson Cancer Center
Nitin Jain
Department of Leukemia, University of Texas MD Anderson Cancer Center
Zeev Estrov
Department of Leukemia, University of Texas MD Anderson Cancer Center
Elias J Jabbour
Department of Leukemia, University of Texas MD Anderson Cancer Center
William G Wierda
Department of Leukemia, University of Texas MD Anderson Cancer Center
Sherry Pierce
Department of Leukemia, University of Texas MD Anderson Cancer Center
Maria Rhona Pinsoy
Department of Leukemia, University of Texas MD Anderson Cancer Center
Lianchun Xiao
Department of Biostatistics, University of Texas MD Anderson Cancer Center
Farhad Ravandi
Department of Leukemia, University of Texas MD Anderson Cancer Center
Jorge E Cortes
Department of Leukemia, University of Texas MD Anderson Cancer Center
FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation in acute myeloid leukemia (AML) is associated with poor prognosis. We hypothesized that quizartinib, a selective and potent FLT3 inhibitor, with azacitidine (AZA) or low-dose cytarabine (LDAC) might improve the outcomes in patients with FLT3-ITD-mutated AML. In this open-label phase I/II trial, patients of any age receiving first-salvage treatment for FLT3-ITD AML or age >60 years with untreated myelodysplastic syndrome or AML were treated with quizartinib plus AZA or LDAC. Seventy-three patients were treated (34 frontline, 39 first-salvage). Among previously untreated patients, composite response (CRc) was achieved in 13/15 (87%, 8 CR, 4 Cri, 1 CRp) treated with quizartinib/AZA and 14/19 (74%, 1 CR, 8 CRi, 5 CRp) in quizartinib/LDAC. The median OS was 19.2 months for quizartinib/AZA and 8.5 months for quizartinib/LDAC cohort; RFS was 10.5 and 6.4 months, respectively. Among previously treated patients, 16 (64%) achieved CRc in quizartinib/AZA and 4 (29%) in quizartinib/LDAC. The median OS for patients treated with quizartinib/AZA and quizartinib/LDAC was 12.8 vs. 4 months, respectively. QTc prolongation grade 3 occurred in only 1 patient in each 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.
