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Blood. 2017 Feb 16;129(7):846-854. doi: 10.1182/blood-2016-09-742205. Epub 2016 Dec 8.

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

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Service d'Hématologie Adulte and INSERM UMRS-1160, Hôpital Saint-Louis, Paris, France.
Service d'Hématologie Clinique, CHU Lyon Sud, Pierre Bénite and INSERM 1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
Laboratoire d'Hématologie, CHU Henri Mondor, Créteil, France.
INSERM CIC 1402, CHU de Poitiers, France.
Service d'Hématologie, CHU Brabois, Vandoeuvre les Nancy, France.
Service des Maladies du Sang, CHRU d'Angers, France.
Service des Maladies du Sang, Hôpital Huriez, CHRU de Lille, France.
Service d'Hématologie Clinique, Hôpital Morvan, CHRU de Brest, France.
Service d'Hématologie Clinique, Hôpital de l'Archet, CHU de Nice, France.
Centre Régional de Lutte Contre le Cancer de Bordeaux et du Sud-Ouest, Bordeaux, France.
Service d'Hématologie, Centre Hospitalier de Dunkerque, France.
Service de Médecine Onco-Hématologie, Centre Hospitalier Départemental Vendée, La Roche sur Yon, France.
Service d'Hématologie Adulte, CHU de Rennes, France.
Service d'Onco-Hématologie, Institut Paoli Calmettes, Marseille, France.
Service d'Hématologie Clinique, CHU de Caen, France; and.
Service d'Hématologie Oncologie et INSERM UMR-1173, Centre Hospitalier de Versailles, Le Chesnay, France.


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.

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