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 |
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| Authors: | 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 Pierce Maria Rhona Pinsoy Lianchun Xiao Farhad Ravandi Jorge E Cortes |
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| Institution: | 1.Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX;2.Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY;3.Department of Hematological Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD;4.Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX;5.Georgia Cancer Center at Augusta University, Augusta, GA, USA |
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| 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. ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT01892371","term_id":"NCT01892371"}}NCT01892371. |
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