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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.

  • Author(s): Atallah, Ehab
  • Schiffer, Charles A
  • Weinfurt, Kevin P
  • Zhang, Mei-Jie
  • Radich, Jerald P
  • Oehler, Vivian G
  • Pinilla-Ibarz, Javier
  • Deininger, Michael WN
  • Lin, Li
  • Larson, Richard A
  • Mauro, Michael J
  • Moore, Joseph O
  • Ritchie, Ellen K
  • Shah, Neil P
  • Silver, Richard T
  • Wadleigh, Martha
  • Cortes, Jorge
  • Thompson, James
  • Guhl, Jessica
  • Horowitz, Mary M
  • Flynn, Kathryn E
  • et al.
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 .

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