title: Long-term outcome of a phase 2 trial with nilotinib 400 mg twice daily in first-line treatment of chronic myeloid leukemia.
abstract: Nilotinib is a second-generation tyrosine kinase inhibitor that has been approved for the first-line treatment of chronic-phase chronic myeloid leukemia, based on the results of a prospective randomized study of nilotinib versus imatinib (ENESTnd). Apart from this registration study, very few data are currently available on first-line nilotinib treatment. We report here the long-term, 6-year results of the first investigator-sponsored, GIMEMA multicenter phase 2, single-arm trial with nilotinib 400 mg twice daily as first-line treatment in 73 patients with chronic-phase chronic myeloid leukemia. Six-year overall survival and progression-free survival rates were 96%, with one death after progression to blast phase. At 6 years, 75% of the patients were still on nilotinib. The cumulative incidence of major molecular response was 98%; only one patient had a confirmed loss of major molecular response. The cumulative incidence of deep molecular response (MR 4.0) was 76%. Deep molecular response was stable (≥ 2 years) in 34% of these patients. Cardiovascular adverse events, mainly due to arterial thrombosis, occurred in 11/73 patients (15%), after 24 to 76 months of therapy. They were more frequent in elderly patients, and in those with baseline cardiovascular risk factors. None was fatal, although there was a relevant morbidity. This is the study with the longest follow-up of a high dose of nilotinib (400 mg twice daily): it highlights the high efficacy and the cardiovascular toxicity of the drug (CTG.NCT.00481052).
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" University Hospital, University of Bologna, Roma, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gugliotta
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" University Hospital, University of Bologna, Roma, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Castagnetti
authors.affiliation: Chair of Hematology, "Sapienza" University, Roma, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.affiliation: Hematology Unit, "Pugliese-Ciaccio" Hospital, Catanzaro, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Levato
authors.affiliation: Hematology Unit, "Spedali Civili" Hospital, Brescia, Ravenna, Italy.
authors.forename: Mariella
authors.initials: M
authors.lastname: D'Adda
authors.affiliation: Chair of Hematology, University of Catania, Ravenna, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Stagno
authors.affiliation: Chair of Hematology, University of Udine, Ravenna, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Tiribelli
authors.affiliation: Hematology Unit, "S. Maria delle Croci" Hospital, Ravenna, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Salvucci
authors.affiliation: Chair of Hematology, Department of Clinical and Biological Sciences, "S. Luigi Gonzaga" University Hospital, University of Torino, Orbassano, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Fava
authors.affiliation: Hematology Unit, "Bianchi-Melacrino-Morelli" Hospital, Reggio Calabria, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Martino
authors.affiliation: Hematology Unit, "S. Giovanni Addolorata" Hospital, Roma, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Cedrone
authors.affiliation: Chair of Hematology, "S. Maria alle Scotte" Hospital, University of Siena, Piacenza, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Bocchia
authors.affiliation: Hematology Unit, "Guglielmo da Saliceto" Hospital, Piacenza, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Trabacchi
authors.affiliation: Chair of Hematology, "S. Anna" University Hospital, University of Ferrara, Cagliari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavazzini
authors.affiliation: Hematology Unit, "A. Businco" Hospital, Cagliari, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Usala
authors.affiliation: Chair of Hematology, University of Bari, Napoli, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Russo Rossi
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" University Hospital, University of Bologna, Roma, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bochicchio
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" University Hospital, University of Bologna, Roma, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Soverini
authors.affiliation: Chair of Hematology, "Sapienza" University, Roma, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Alimena
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" University Hospital, University of Bologna, Roma, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
authors.affiliation: Chair of Hematology, Department of Biochemistry and Medical Biotechnologies, "Federico II" University, Napoli, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pane
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" University Hospital, University of Bologna, Roma, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.affiliation: Chair of Hematology, Department of Clinical and Biological Sciences, "S. Luigi Gonzaga" University Hospital, University of Torino, Orbassano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.affiliation: Department of Hematology and Oncology "L. and A. Seràgnoli", University of Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" University Hospital, University of Bologna, Roma, Italy gianantonio.rosti@unibo.it.
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
mesh_terms: D000328:Adult; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D011743:Pyrimidines / Q000008:administration & dosage*; D015996:Survival Rate
chemical_list: D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib