Open AccessA 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
Author(s) -
Mahesh Swaminathan,
Hagop M. Kantarjian,
Mark J. Levis,
Veronica Guerra,
Gautam Borthakur,
Yesid Alvarado,
Courtney D. DiNardo,
Tapan M. Kadia,
Guillermo GarciaManero,
Maro Ohanian,
Naval Daver,
Marina Konopleva,
Naveen Pemmaraju,
Alessandra Ferrajoli,
Michael Andreeff,
Nitin Jain,
Zeev Estrov,
Elias Jabbour,
William G. Wierda,
Sherry Pierce,
Maria Rhona Pinsoy,
Lianchun Xiao,
Farhad Ravandi,
Jorge Cortes
Publication year - 2021
Publication title -
haematologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.782
H-Index - 142
eISSN - 1592-8721
pISSN - 0390-6078
DOI - 10.3324/haematol.2020.263392
Subject(s) - medicine , cytarabine , myeloid leukemia , oncology , azacitidine , gastroenterology , biochemistry , gene expression , chemistry , dna methylation , gene
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.