Randomised evaluation of quizartinib and low-dose ara-C vs low-dose ara-C in older acute myeloid leukemia patients

Dennis, M. et al. (2021) Randomised evaluation of quizartinib and low-dose ara-C vs low-dose ara-C in older acute myeloid leukemia patients. Blood Advances, 5(24), pp. 5621-5625. (doi: 10.1182/bloodadvances.2021005038) (PMID:34597366) (PMCID:PMC8714727)

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Survival for older patients with acute myeloid leukaemia (AML) unsuitable for intensive chemotherapy is unsatisfactory. Standard non intensive 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 randomised 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=0.05) with CR/CRi for quizartinib + LDAC in 5/13 (38%) v 0/14 (0%) in patients receiving LDAC alone. Overall survival (OS) in these FLT3-ITD positive patients was also significantly improved at 2 years for quizartinib + LDAC; hazard ratio 0.36 (95% confidence intervals 0.16, 0.85), (p=0.04). Median OS was 13.7 months compared to 4.2 months with LDAC alone. This is the first report of a FLT3 targeted therapy added to standard non-intensive chemotherapy that has improved survival in this population. Quizartinib merits consideration for future triplet based treatment approaches. (Clinical trial numbers: ISRCTN No: ISRCTN40571019 EUDRACT Number: 2011-000749-19).

Item Type:Articles
Glasgow Author(s) Enlighten ID:Copland, Professor Mhairi and Burnett, Professor Alan
Authors: Dennis, M., Thomas, I. F., Ariti, C., Upton, L., Burnett, A. K., Gilkes, A., Radia, R., Hemmaway, C., Mehta, P., Knapper, S., Clark, R. E., Copland, M., Russell, N., and Hills, R. K.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Blood Advances
Publisher:American Society of Hematology
ISSN (Online):2473-9537
Published Online:01 October 2021
Copyright Holders:Copyright © 2021 American Society of Hematology
First Published:First published in Blood Advances 5(24): 5621-5625
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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