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Design and rationale for the life after stopping tyrosine kinase inhibitors (LAST) study, a prospective, single-group longitudinal study in patients with chronic myeloid leukemia. BMC Cancer 2018 04 02;18(1):359

Date

04/04/2018

Pubmed ID

29609532

Pubmed Central ID

PMC5879565

DOI

10.1186/s12885-018-4273-1

Scopus ID

2-s2.0-85044841612   9 Citations

Abstract

BACKGROUND: Treatment of chronic myeloid leukemia with a tyrosine kinase inhibitor (TKI) offers significant improvements over previous treatments in terms of survival and toxicity yet nevertheless is associated with reduced health-related quality of life and very high cost. Several small studies from Europe and Australia suggested that discontinuing TKIs with regular monitoring was safe.

METHODS: The Life After Stopping TKIs (LAST) study is a large, U.S.-based study that aims to improve the evidence for clinical decision making regarding TKI discontinuation with monitoring in patients with chronic myeloid leukemia who have a deep molecular response to TKI therapy. The LAST study is a non-randomized, prospective, single-group longitudinal study of 173 patients. The co-primary objectives are to determine the proportion of patients who develop molecular recurrence (>‚ÄČ0.1% BCR-ABLIS) after discontinuing one of four TKIs (imatinib, dasatinib, nilotinib, or bosutinib) and to compare the patient-reported health status of patients before and after stopping TKIs. Outcomes are assessed at baseline and throughout the 36-month study follow-up period with a central laboratory used for blood samples. All samples with undetectable BCR-ABL are also examined using digital polymerase chain reaction, which is a more sensitive nanofluidic polymerase chain reaction system.

DISCUSSION: Because of their high cost and side effects, discontinuation of TKIs for patients with chronic myeloid leukemia who have a deep molecular response to TKI therapy is a promising approach to treatment. The LAST study is the largest U.S.-based TKI discontinuation study. It is the first to allow participation from patients on any of 4 first- and second-generation TKIs, includes a robust approach to measurement of clinical and patient-reported outcomes, and is using digital polymerase chain reaction to explore better prediction of safe discontinuation.

TRIAL REGISTRATION: This study was registered prospectively on October 21, 2014 and assigned trial number NCT02269267 .

Author List

Atallah E, Schiffer CA, Weinfurt KP, Zhang MJ, Radich JP, Oehler VG, Pinilla-Ibarz J, Deininger MWN, Lin L, Larson RA, Mauro MJ, Moore JO, Ritchie EK, Shah NP, Silver RT, Wadleigh M, Cortes J, Thompson J, Guhl J, Horowitz MM, Flynn KE

Authors

Ehab L. Atallah MD Professor in the Medicine department at Medical College of Wisconsin
Kathryn Eve Flynn PhD Professor in the Medicine department at Medical College of Wisconsin
Mary M. Horowitz MD, MS Center Director, Professor in the Medicine department at Medical College of Wisconsin
Jonathan R. Thompson MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Mei-Jie Zhang PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Antineoplastic Agents
Clinical Protocols
Fusion Proteins, bcr-abl
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Longitudinal Studies
Molecular Targeted Therapy
Patient Reported Outcome Measures
Protein Kinase Inhibitors
Quality of Life
Recurrence
Research Design
Watchful Waiting
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0