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. HorowitzKathryn E. Flynn

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number359
JournalBMC Cancer
Volume18
Issue number1
DOIs
StatePublished - Apr 2 2018

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Longitudinal Studies
Prospective Studies
Polymerase Chain Reaction
Therapeutics
Patient Participation
Costs and Cost Analysis
Physiologic Monitoring
Health Status
Quality of Life
Recurrence
Survival

Keywords

  • Chronic myeloid leukemia
  • Clinical trial
  • Discontinuation
  • Oncology
  • Patient-reported outcome
  • Study design
  • Targeted therapy
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

Cite this

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. / Atallah, Ehab; Schiffer, Charles A.; Weinfurt, Kevin P.; Zhang, Mei Jie; Radich, Jerald P.; Oehler, Vivian G.; Pinilla-Ibarz, Javier; Deininger, Michael W.N.; 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.

In: BMC Cancer, Vol. 18, No. 1, 359, 02.04.2018.

Research output: Contribution to journalArticle

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 2018, '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, vol. 18, no. 1, 359. https://doi.org/10.1186/s12885-018-4273-1
Atallah, Ehab ; Schiffer, Charles A. ; Weinfurt, Kevin P. ; Zhang, Mei Jie ; Radich, Jerald P. ; Oehler, Vivian G. ; Pinilla-Ibarz, Javier ; Deininger, Michael W.N. ; 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. / 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. In: BMC Cancer. 2018 ; Vol. 18, No. 1.
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AU - Atallah, Ehab

AU - Schiffer, Charles A.

AU - Weinfurt, Kevin P.

AU - Zhang, Mei Jie

AU - Radich, Jerald P.

AU - Oehler, Vivian G.

AU - Pinilla-Ibarz, Javier

AU - Deininger, Michael W.N.

AU - Lin, Li

AU - Larson, Richard A.

AU - Mauro, Michael J.

AU - Moore, Joseph O.

AU - Ritchie, Ellen K.

AU - Shah, Neil P.

AU - Silver, Richard T.

AU - Wadleigh, Martha

AU - Cortes, Jorge

AU - Thompson, James

AU - Guhl, Jessica

AU - Horowitz, Mary M.

AU - Flynn, Kathryn E.

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N2 - 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.

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