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World J Clin Oncol. Dec 24, 2020; 11(12): 996-1007
Published online Dec 24, 2020. doi: 10.5306/wjco.v11.i12.996
Predictive indicators of successful tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia
Ruth Stuckey, Juan Francisco López-Rodríguez, Santiago Sánchez-Sosa, Adrián Segura-Díaz, Nuria Sánchez-Farías, Cristina Bilbao-Sieyro, María Teresa Gómez-Casares
Ruth Stuckey, Juan Francisco López-Rodríguez, Santiago Sánchez-Sosa, Adrián Segura-Díaz, Nuria Sánchez-Farías, Cristina Bilbao-Sieyro, María Teresa Gómez-Casares, Department of Hematology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria 35019, Spain
Author contributions: Stuckey R and López-Rodríguez JF wrote the review; Sánchez-Sosa S updated the CML registry and patient data; Segura-Díaz A and Gómez-Casares MT treated patients with CML; Stuckey R, Sánchez-Sosa S, and Sánchez-Farías N coordinated TKI discontinuation clinical trials; Bilbao-Sieyro C and Gómez-Casares MT supervised the investigational and medical aspects, respectively, of discontinuation studies at our center; All authors approved the final version of the manuscript.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: María Teresa Gomez-Casares, MD, PhD, Chief Doctor, Department of Hematology, Hospital Universitario de Gran Canaria Dr. Negrín, Barranco de la Ballena s/n, Las Palmas de Gran Canaria 35019, Spain. mgomcasf@gobiernodecanarias.org
Received: March 21, 2020
Peer-review started: March 21, 2020
First decision: September 24, 2020
Revised: September 28, 2020
Accepted: October 21, 2020
Article in press: October 21, 2020
Published online: December 24, 2020
Abstract

Clinical trials have demonstrated that some patients with chronic myeloid leukemia (CML) treated for several years with tyrosine kinase inhibitors (TKIs) who have maintained a molecular response can successfully discontinue treatment without relapsing. Treatment free remission (TFR) can be reached by approximately 50% of patients who discontinue. Despite having similar levels of deep molecular response and an identical duration of treatment, the factors that influence the successful discontinuation of CML patients remain to be determined. In this review we will explore the factors identified to date that can help predict whether a patient will successfully achieve TFR. We will also discuss the need for the identification of predictive biomarkers associated with a high probability of achieving TFR for the future personalized identification of patients who are suitable for the discontinuation of TKI treatment.

Keywords: Biomarkers, Tyrosine kinase inhibitors, Treatment discontinuation, Molecular monitoring, Duration of therapy, Leukemia, Myelogenous, Chronic, BCR-ABL positive

Core Tip: Clinical trials have shown that approximately 50% of patients with chronic myeloid leukemia who reach a deep molecular response (MR) following treatment for several years with tyrosine kinase inhibitors (TKI) can discontinue and remain in treatment-free remission (TFR). Factors such as the duration of TKI treatment and duration and depth of the patient’s MR prior to discontinuation appear to be important in determining whether TFR is achieved. However, it is clear that other biological factors must determine whether an individual will remain in TFR after discontinuation. Future studies should aim to elucidate biomarkers predictive of TFR.