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Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study

Delphine Rea, Franck E. Nicolini, Michel Tulliez, François Guilhot, Joelle Guilhot, Agnès Guerci-Bresler, Martine Gardembas, Valérie Coiteux, Gaelle Guillerm, Laurence Legros, Gabriel Etienne, Jean-Michel Pignon, Bruno Villemagne, Martine Escoffre-Barbe, Jean-Christophe Ianotto, Aude Charbonnier, Hyacinthe Johnson-Ansah, Marie-Pierre Noel, Philippe Rousselot, François-Xavier Mahon and for the France Intergroupe des Leucémies Myéloïdes Chroniques

Key Points

  • First-line or subsequent dasatinib or nilotinib can be safely stopped in CML patients with deep and long-lasting molecular responses.

  • A suboptimal response or resistance prior to dasatinib or nilotinib is associated with significantly worse treatment-free remission.

Publisher's Note: There is an Inside Blood Commentary on this article in this issue.

Abstract

STOP second generation (2G)–tyrosine kinase inhibitor (TKI) is a multicenter observational study designed to evaluate 2G-TKI discontinuation in chronic myeloid leukemia (CML). Patients receiving first-line or subsequent dasatinib or nilotinib who stopped therapy after at least 3 years of TKI treatment and in molecular response 4.5 (MR4.5) with undetectable BCR-ABL1 transcripts for the 2 preceding years at least were eligible for inclusion. This interim analysis reports outcomes of 60 patients with a minimum follow-up of 12 months (median 47, range: 12-65). Twenty-six patients (43.3%) experienced a molecular relapse defined as the loss of a major molecular response (MMR). Relapses occurred after a median time of 4 months (range: 1-38). Cumulative incidences of molecular relapse by 12 and 48 months were 35% (95% confidence interval [CI], 24.79% to 49.41%) and 44.76% (95% CI, 33.35% to 59.91%), respectively. Treatment-free remission (TFR) rates at 12 and 48 months were 63.33% (95% CI, 51.14% to 75.53%) and 53.57% (95% CI, 40.49% to 66.65%), respectively. In univariate analysis, prior suboptimal response or TKI resistance was the only baseline factor associated with significantly worse outcome. A landmark analysis demonstrated that loss of MR4.5 3 months after stopping TKI was predictive of failure to maintain MMR later on. During the treatment-free phase, no progression toward advanced phase CML occurred, and all relapsing patients regained MMR and MR4.5 after restarting therapy. In conclusion, discontinuation of first-line or subsequent 2G-TKI yields promising TFR rates without safety concerns. Further research is encouraged to better define conditions that will offer patients the highest chance to remain free from 2G-TKI therapy.

  • Submitted September 26, 2016.
  • Accepted November 28, 2016.
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