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.

Published online

Journal Article

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 .

Full Text

Duke Authors

Cited Authors

  • Atallah, E; Schiffer, CA; Weinfurt, KP; Zhang, M-J; 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

Published Date

  • April 2, 2018

Published In

Volume / Issue

  • 18 / 1

Start / End Page

  • 359 -

PubMed ID

  • 29609532

Pubmed Central ID

  • 29609532

Electronic International Standard Serial Number (EISSN)

  • 1471-2407

Digital Object Identifier (DOI)

  • 10.1186/s12885-018-4273-1

Language

  • eng

Conference Location

  • England