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Emergence of BCR-ABL kinase domain mutations associated with newly diagnosed chronic myeloid leukemia: a meta-analysis of clinical trials of tyrosine kinase inhibitors.

Abstract：

BACKGROUND:Tyrosine kinase inhibitors (TKIs) are a mainstay of treatment for patients suffering from chronic myeloid leukemia (CML). Testing for various mutations in the BCR-ABL gene may help predict lack of response to specific TKIs where resistance has developed. OBJECTIVE:To estimate the emergence of BCR-ABL kinase domain mutations associated with newly diagnosed CML patients exposed to first-line TKI treatment. METHODS:Published studies were identified using a structured search of online databases. Original research studies were included if they reported the incidence of specific BCR-ABL kinase domain point mutations after first-line TKI treatment failure or baseline mutations for second-line TKI treatment following first-line treatment failure. Meta-analysis of mutation rates across studies was based on DerSimonian and Laird's random-effects model. RESULTS:Of 1,323 citations, 12 studies met the inclusion criteria, involving a total of 1,698 patients. Overall mutation rates (95% CI) were imatinib 9.7% (6.2%-13.3%); dasatanib 1.7% (0.0%-4.3%); and nilotinib 3.3% (0.0%-7.7%). The most common specific mutations were T315I, E255K, and M351T. T315I mutations constituted 58% (7 of 12) of dasatinib-related mutations and 13% (15 of 117) of imatinib-related mutations. CONCLUSIONS:Lack of response to TKIs associated with mutation in the BCR-ABL gene was significantly higher in imatinib-treated patients, and all mutations arose after treatment. T315I was a common treatment-emergent mutation. Further research is needed to assess the prognostic value of testing for mutations and the economic implications of treatment-emergent mutations.

journal_name

J Manag Care Spec Pharm

journal_title

Journal of managed care & specialty pharmacy

authors

Ursan ID,Jiang R,Pickard EM,Lee TA,Ng D,Pickard AS

doi

10.18553/jmcp.2015.21.2.114

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

114-22

issue

eissn

2376-0540

issn

2376-1032

pii

2015(21)2: 114-122

journal_volume

pub_type

杂志文章,meta分析

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Emergence of BCR-ABL kinase domain mutations associated with newly diagnosed chronic myeloid leukemia: a meta-analysis of clinical trials of tyrosine kinase inhibitors.