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 and François-Xavier Mahon

Key points

  • 1st or subsequent line 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.


STOP 2G-TKI is a multicenter observational study designed to evaluate 2nd generation (2G)-tyrosine kinase inhibitor (TKI) discontinuation in chronic myeloid leukemia (CML). Patients receiving 1st or subsequent line 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% CI; 24.79%-49.41%) and 44.76% (95% CI; 33.35%-59.91%), respectively. Treatment-free remission (TFR) rates at 12 and 48 months were 63.33% (95% CI; 51.14%-75.53%) and 53.57% (95% CI; 40.49%-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. To conclude, discontinuation of 1st or subsequent line 2G-TKI yields promising TFR rates without safety concerns. Further research is encouraged to better define conditions that will offer patients highest chances to remain free from 2G-TKI therapy.

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