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

Dennis, Mike, Thomas, Ian F., Ariti, Cono, Upton, Laura, Burnett, Alan K., Gilkes, Amanda, Radia, Rohini, Hemmaway, Claire, Mehta, Priyanka, Knapper, Steven, Clark, Richard E., Copland, Mhairi, Russell, Nigel and Hills, Robert K. 2021. Randomized 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. 10.1182/bloodadvances.2021005038

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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 5 .05) with complete remission/complete remission with incomplete haematological recovery for quizartinib 1 LDAC in 5/13 (38%) vs 0/14 (0%) in patients receiving LDAC alone. Overall survival (OS) in these FLT3-ITD1 patients was also significantly improved at 2 years for quizartinib 1 LDAC (hazard ratio 0.36; 95% confidence intervals: 0.16, 0.85, P 5 .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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Centre for Trials Research (CNTRR)
Additional Information:	Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only non commercial, non derivative use with attribution
Publisher:	American Society of Hematology
ISSN:	2473-9529
Date of First Compliant Deposit:	18 February 2022
Date of Acceptance:	2 August 2021
Last Modified:	26 Feb 2022 12:00
URI:	https://orca.cardiff.ac.uk/id/eprint/147678

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