1. Randomized evaluation of quizartinib and low-dose ara-C vs low-dose ara-C in older acute myeloid leukemia patients
- Author
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Mhairi Copland, Ian Thomas, Nigel H. Russell, Richard E. Clark, Robert Kerrin Hills, Cono Ariti, Priyanka Mehta, Michael Dennis, Steven Knapper, Laura Upton, Rohini Radia, Amanda F. Gilkes, Claire Hemmaway, and Alan K. Burnett
- Subjects
Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Population ,Targeted therapy ,chemistry.chemical_compound ,fluids and secretions ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Humans ,Benzothiazoles ,education ,Quizartinib ,Aged ,Chemotherapy ,education.field_of_study ,business.industry ,Phenylurea Compounds ,Hazard ratio ,Cytarabine ,Myeloid leukemia ,hemic and immune systems ,Hematology ,Stimulus Report ,Confidence interval ,Clinical trial ,Leukemia, Myeloid, Acute ,chemistry ,embryonic structures ,business ,psychological phenomena and processes - Abstract
Key Points First report of an FLT3-targeted therapy added to nonintensive chemotherapy that has improved survival in older FLT3-ITD patients with AML.Quizartinib is well tolerated, improves response and survival in older FLT3-ITD AML patients and merits consideration in future therapies. Now amended as text above., Visual Abstract, Survival for older patients with acute myeloid leukemia (AML) unsuitable for intensive chemotherapy is unsatisfactory. Standard nonintensive therapies have low response rates and only extend life by a few months. Quizartinib is an oral Fms-like tyrosine kinase 3 (FLT3) inhibitor with reported activity in wild-type patients. As part of the AML LI trial, we undertook a randomized evaluation of low-dose ara-C (LDAC) with or without quizartinib in patients not fit for intensive chemotherapy. Overall, survival was not improved (202 patients), but in the 27 FLT3-ITD patients, the addition of quizartinib to LDAC improved response (P = .05) with complete remission/complete remission with incomplete haematological recovery for quizartinib + LDAC in 5/13 (38%) vs 0/14 (0%) in patients receiving LDAC alone. Overall survival (OS) in these FLT3-ITD+ patients was also significantly improved at 2 years for quizartinib + LDAC (hazard ratio 0.36; 95% confidence intervals: 0.16, 0.85, P = .04). Median OS was 13.7 months compared with 4.2 months with LDAC alone. This is the first report of an FLT3-targeted therapy added to standard nonintensive chemotherapy that has improved survival in this population. Quizartinib merits consideration for future triplet-based treatment approaches. This trial was registered at www.clinicaltrials.gov as ISRCTN #ISRCTN40571019 and EUDRACT @2011-000749-19.
- Published
- 2021