What are the considerations for tyrosine kinase inhibitor discontinuation in chronic-phase chronic myeloid leukemia?

ABSTRACT

Introduction: The outlook for patients with chronic myeloid leukemia (CML) has changed dramatically with the development of tyrosine kinase inhibitors (TKIs) with the current treatment goal for many patients being to obtain a durable deep molecular remission, discontinue TKI therapy, and remain treatment free.

Areas covered: In this article, the authors review the data from the major TKI discontinuation studies, explore potential predictors of discontinuation outcome and look at possible mechanisms to explain the variable outcomes following TKI discontinuation including immune surveillance and leukemic stem cell (LSC) depletion following TKI treatment. Data from relevant articles published on the Pubmed database between January 2007 and January 2020 have been included.

Expert opinion: The results from the majority of TKI discontinuation studies show a consistent picture with approximately half of eligible patients achieving treatment free remission (TFR). However, reliable clinical predictors or biomarkers for the outcome of TKI discontinuation remain elusive and the mechanisms to explain the diversity of discontinuation success are not completely understood. Future studies will need to focus on attempts to increase the number of patients eligible for treatment discontinuation and will likely involve drug combinations including novel agents aimed at targeting the residual LSC population and enhancement of immune surveillance mechanisms.

KEYWORDS:

• Chronic myeloid leukemia
• TKI discontinuation
• treatment-free remission
• immune surveillance

Article highlights

• Comprehensive review of data from major TKI discontinuation studies.

• Practical guidance on monitoring following a TKI discontinuation attempt.

• Clinical predictors of TKI discontinuation outcome.

• Potential biological predictors of TKI discontinuation outcome

• Focus on potential mechanisms to explain maintained treatment-free remission.

Declaration of interest

P Harrington has received research funding from Bristol Myers Squibb; D Radia has been on the education and advisory boards for Novartis and the advisory board for Blueprint Medicine; H de Lavallade has received research funding from Bristol Myers Squibb and INCyte and has received honoraria from Novartis, Pfizer, Bristol Myers Squibb, and INCyte. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This article was not funded.