title: Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study.
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 undetectableBCR-ABL1transcripts 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.
authors.affiliation: Service d'Hématologie Adulte and INSERM UMRS-1160, Hôpital Saint-Louis, Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Rea
authors.affiliation: Service d'Hématologie Clinique, CHU Lyon Sud, Pierre Bénite and INSERM 1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors.forename: Franck E
authors.initials: FE
authors.lastname: Nicolini
authors.affiliation: Laboratoire d'Hématologie, CHU Henri Mondor, Créteil, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Tulliez
authors.affiliation: INSERM CIC 1402, CHU de Poitiers, France.
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
authors.affiliation: INSERM CIC 1402, CHU de Poitiers, France.
authors.forename: Joelle
authors.initials: J
authors.lastname: Guilhot
authors.affiliation: Service d'Hématologie, CHU Brabois, Vandoeuvre les Nancy, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Guerci-Bresler
authors.affiliation: Service des Maladies du Sang, CHRU d'Angers, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Gardembas
authors.affiliation: Service des Maladies du Sang, Hôpital Huriez, CHRU de Lille, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Coiteux
authors.affiliation: Service d'Hématologie Clinique, Hôpital Morvan, CHRU de Brest, France.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Guillerm
authors.affiliation: Service d'Hématologie Clinique, Hôpital de l'Archet, CHU de Nice, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Legros
authors.affiliation: Centre Régional de Lutte Contre le Cancer de Bordeaux et du Sud-Ouest, Bordeaux, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Etienne
authors.affiliation: Service d'Hématologie, Centre Hospitalier de Dunkerque, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pignon
authors.affiliation: Service de Médecine Onco-Hématologie, Centre Hospitalier Départemental Vendée, La Roche sur Yon, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Villemagne
authors.affiliation: Service d'Hématologie Adulte, CHU de Rennes, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Escoffre-Barbe
authors.affiliation: Service d'Hématologie Clinique, Hôpital Morvan, CHRU de Brest, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Ianotto
authors.affiliation: Service d'Onco-Hématologie, Institut Paoli Calmettes, Marseille, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Charbonnier
authors.affiliation: Service d'Hématologie Clinique, CHU de Caen, France; and.
authors.forename: Hyacinthe
authors.initials: H
authors.lastname: Johnson-Ansah
authors.affiliation: Service des Maladies du Sang, Hôpital Huriez, CHRU de Lille, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Noel
authors.affiliation: Service d'Hématologie Oncologie et INSERM UMR-1173, Centre Hospitalier de Versailles, Le Chesnay, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
authors.affiliation: Centre Régional de Lutte Contre le Cancer de Bordeaux et du Sud-Ouest, Bordeaux, France.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Mahon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000069439:Dasatinib / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D015994:Incidence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib; D000069439:Dasatinib