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

被引：20

作者：

Dennis, Mike ^{[1
]}

Thomas, Ian F. ^{[2
]}

Ariti, Cono ^{[2
]}

Upton, Laura ^{[2
]}

Burnett, Alan K. ^{[3
]}

Gilkes, Amanda ^{[2
]}

Radia, Rohini ^{[4
]}

Hemmaway, Claire ^{[5
]}

Mehta, Priyanka ^{[6
,7
]}

Knapper, Steven ^{[2
]}

Clark, Richard E. ^{[8
]}

Copland, Mhairi ^{[3
]}

Russell, Nigel ^{[4
]}

Hills, Robert K. ^{[9
]}

机构：

[1] Christie, Manchester, Lancs, England

[2] Cardiff Univ, Ctr Trials Res, Cardiff, Wales

[3] Univ Glasgow, Inst Canc Sci, Glasgow, Lanark, Scotland

[4] Nottingham Univ Hosp, Dept Haematol, Nottingham, England

[5] Auckland Dist Hlth Board, Auckland, New Zealand

[6] Queens Hosp, Dept Haematol, Romford, Essex, England

[7] Univ Hosp Bristol, Dept Haematol, Bristol, Avon, England

[8] Univ Liverpool, Dept Mol & Clin Canc Med, Liverpool, Merseyside, England

[9] Nuffield Dept Populat Hlth, Oxford, England

来源：

BLOOD ADVANCES | 2021年 / 5卷 / 24期

关键词：

AZACITIDINE; MUTATIONS; THERAPY;

D O I：

10.1182/bloodadvances.2021005038

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：5621 / 5625

页数：5

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