The Importance of Mutational Analysis in Chronic Myeloid Leukaemia for Treatment Choice

*Hugues de Lavallade,1,3 Aytug Kizilors2,3

1. Department of Haematological Medicine, King’s College Hospital NHS Foundation Trust, London, UK
2. Laboratory for Molecular Haemato-Oncology, King’s College Hospital NHS Foundation Trust/King’s College London, London, UK
3. Haematology Department, King’s College London, London, UK
*Correspondence to h.delavallade@nhs.net

Disclosure: Hugues de Lavallade received research funding from Ariad Pharma and consultancy fees from Novartis. Aytug Kizilors has received research funding from Ariad Pharma.
Support: The publication of this article was funded by Incyte Biosciences. The views and opinions expressed are those of the authors and not necessarily of Incyte Biosciences.
Received: 03.03.16 Accepted: 16.06.16
Citation: EMJ Oncol. 2016;4[1]:86-95.

Abstract

Since their introduction in 2001, tyrosine kinase inhibitors (TKIs) targeting BCR-ABL have become the standard therapy for chronic myeloid leukaemia (CML). While allogeneic hematopoietic stem cell transplant is a recognised curative treatment for CML, TKIs prevent progression to advanced phase in most patients, and spectacularly improve the disease burden (in deep molecular responders) and the overall survival of CML patients.

However, mutations in the BCR-ABL kinase domain affect a significant proportion of CML patients and have been associated with primary or secondary (refractory disease following an initial response) resistance to imatinib. Such resistance may emerge at any time during TKI therapy and are a major mechanism of treatment failure, in addition to BCR-ABL-independent treatment resistance and treatment intolerance mechanisms. In the context of the above-described clinical settings, the management of CML patients remains challenging. The detection of mutations following imatinib resistance is therefore crucial to ensure appropriate second or third-line drug selection.

This article has a correction, made on 13.02.17.
The details of the correction are as follows: Extensive changes.
The prior version of the paper is available on request, please contact editor@emjreviews.com

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