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
Ehab Atallah,
Charles A. Schiffer,
Kevin P. Weinfurt,
Mei-Jie Zhang,
Jerald P. Radich,
Vivian G. Oehler,
Javier Pinilla-Ibarz,
Michael W. N. Deininger,
Li Lin,
Richard A. Larson,
Michael J. Mauro,
Joseph O. Moore,
Ellen K. Ritchie,
Neil P. Shah,
Richard T. Silver,
Martha Wadleigh,
Jorge Cortes,
James Thompson,
Jessica Guhl,
Mary M. Horowitz,
Kathryn E. Flynn
Affiliations
Ehab Atallah
Department of Medicine, Medical College of Wisconsin
Charles A. Schiffer
Karmanos Cancer Institute, Wayne State University School of Medicine
Kevin P. Weinfurt
Department of Population Health Sciences, Duke University School of Medicine
Mei-Jie Zhang
Division of Biostatistics, Medical College of Wisconsin
Jerald P. Radich
Clinical Research Division, Fred Hutchinson Cancer Research Center
Vivian G. Oehler
Clinical Research Division, Fred Hutchinson Cancer Research Center
Javier Pinilla-Ibarz
Department of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute
Michael W. N. Deininger
Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, The University of Utah
Li Lin
Department of Population Health Sciences, Duke University School of Medicine
Richard A. Larson
Department of Medicine and Comprehensive Cancer Center, University of Chicago
Michael J. Mauro
Memorial Sloan Kettering Cancer Center
Joseph O. Moore
Duke Cancer Institute
Ellen K. Ritchie
Weill Medical College of Cornell University
Neil P. Shah
Department of Medicine, University of California at San Francisco
Richard T. Silver
Weill Medical College of Cornell University
Martha Wadleigh
Department of Medical Oncology, Dana-Farber Cancer Institute
Jorge Cortes
University of Texas MD Anderson Cancer Center
James Thompson
Roswell Park Cancer Institute
Jessica Guhl
Cancer Center, Medical College of Wisconsin
Mary M. Horowitz
Department of Medicine, Medical College of Wisconsin
Kathryn E. Flynn
Department of Medicine, Medical College of Wisconsin
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 (> 0.1% 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.
