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 or 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 Ferrajol, Michael Andreeff, Nitin Jain, Zeev Estrov, Elias J. Jabbour, William G. Wierda, Sherry PierceMaria Rhona Pinsoy, Lianchun Xiao, Farhad Ravandi, Jorge E. Cortes

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The 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). With regard to previously untreated patients, the composite response (CRc) rate was 87% (n=13/15: 8 complete responses [CR], 4 CR with incomplete hematologic recovery [CRi], 1 CR without platelet recovery [CRp]) among the patients treated with quizartinib/AZA and 74% (n=14/19: 1 CR, 8 CRi, 5 CRp) among those treated with quizartinib/LDAC. The median overall survival was 19.2 months for the cohort treated with quizartinib/AZA cohort and 8.5 months for the patients treated with quizartinib/LDAC; the corresponding relapse-free survival figures were 10.5 and 6.4 months, respectively. With regard to previously treated patients, the CRc rate was 64% (n=16/25 in the quizartinib/AZA cohort and 29% (n=4/14)) in the quizartinib/LDAC cohort. The median overall survival for patients treated with quizartinib/AZA and quizartinib/LDAC was 12.8 versus 4 months, respectively. QTc prolongation grade 3 occurred in only one patient in each cohort. Quizartinib-based combinations, particularly with AZA, appear effective in both frontline and first salvage therapy for patients with FLT3-ITD-mutated AML and are well tolerated.

Original languageEnglish (US)
Pages (from-to)2121-2130
Number of pages10
JournalHaematologica
Volume106
Issue number8
DOIs
StatePublished - Aug 2021

ASJC Scopus subject areas

  • Hematology

Fingerprint

Dive into the research topics of '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 or myelodysplastic syndrome'. Together they form a unique fingerprint.

Cite this