Format

Send to

Choose Destination
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.

Author information

1
Service d'Hématologie Adulte and INSERM UMRS-1160, Hôpital Saint-Louis, Paris, France.
2
Service d'Hématologie Clinique, CHU Lyon Sud, Pierre Bénite and INSERM 1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
3
Laboratoire d'Hématologie, CHU Henri Mondor, Créteil, France.
4
INSERM CIC 1402, CHU de Poitiers, France.
5
Service d'Hématologie, CHU Brabois, Vandoeuvre les Nancy, France.
6
Service des Maladies du Sang, CHRU d'Angers, France.
7
Service des Maladies du Sang, Hôpital Huriez, CHRU de Lille, France.
8
Service d'Hématologie Clinique, Hôpital Morvan, CHRU de Brest, France.
9
Service d'Hématologie Clinique, Hôpital de l'Archet, CHU de Nice, France.
10
Centre Régional de Lutte Contre le Cancer de Bordeaux et du Sud-Ouest, Bordeaux, France.
11
Service d'Hématologie, Centre Hospitalier de Dunkerque, France.
12
Service de Médecine Onco-Hématologie, Centre Hospitalier Départemental Vendée, La Roche sur Yon, France.
13
Service d'Hématologie Adulte, CHU de Rennes, France.
14
Service d'Onco-Hématologie, Institut Paoli Calmettes, Marseille, France.
15
Service d'Hématologie Clinique, CHU de Caen, France; and.
16
Service d'Hématologie Oncologie et INSERM UMR-1173, Centre Hospitalier de Versailles, Le Chesnay, France.

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.

PMID:
27932374
DOI:
10.1182/blood-2016-09-742205
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center