Dennis, Mike, Thomas, Ian F, Ariti, Cono, Upton, Laura, Burnett, Alan K, Gilkes, Amanda, Radia, Rohini, Hemmaway, Claire, Mehta, Priyanka, Knapper, Steven et al (show 5 more authors)
(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.
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Phenylurea Compounds, Cytarabine, Aged, Benzothiazoles, Leukemia, Myeloid, Acute |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 24 May 2022 08:30 |
| Last Modified: | 18 Jan 2023 21:01 |
| DOI: | 10.1182/bloodadvances.2021005038 |
| Open Access URL: | https://doi.org/10.1182/bloodadvances.2021005038 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3155388 |
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