title: Rotation of nilotinib and imatinib for first-line treatment of chronic phase chronic myeloid leukemia.
abstract: The introduction of second-generation tyrosine-kinase inhibitors (TKIs) has generated a lively debate on the choice of first-line TKI in chronic phase, chronic myeloid leukemia (CML). Despite the TKIs have different efficacy and toxicity profiles, the planned use of two TKIs has never been investigated. We report on a phase 2 study that was designed to evaluate efficacy and safety of a treatment alternating nilotinib and imatinib, in newly diagnosed BCR-ABL1 positive, chronic phase, CML patients. One hundred twenty-three patients were enrolled. Median age was 56 years. The probabilities of achieving a complete cytogenetic response, a major molecular response, and a deep molecular response (MR 4.0) by 2 years were 93%, 87%, and 61%, respectively. The 5-year overall survival and progression-free survival were 89%. Response rates and survival are in the range of those reported with nilotinib alone. Moreover, we observed a relatively low rate of cardiovascular adverse events (5%). These data show that the different efficacy and toxicity profiles of TKIs could be favorably exploited by alternating their use. Am. J. Hematol. 91:617-622, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" Hospital, University of Bologna, Bologna, 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" Hospital, University of Bologna, Bologna, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Castagnetti
authors.affiliation: Chair of Hematology, "Sapienza" University, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.affiliation: Chair of Hematology, "Careggi" Hospital, University of Florence, Florence, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Gozzini
authors.affiliation: Hematology Unit, "A. Businco" Hospital, Cagliari, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Usala
authors.affiliation: IRCCS AOU San Martino-IST, Hematology and Bone Marrow Transplantation Unit, Genova, Italy.
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Carella
authors.affiliation: Chair of Hematology, Department of Clinical and Biological Sciences, "S. Luigi Gonzaga" University Hospital, University of Torino, Orbassano, (Torino), Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rege-Cambrin
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. Eugenio" Hospital, Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Abruzzese
authors.affiliation: Chair of Hematology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Albano
authors.affiliation: Chair of Hematology, "Ferrarotto" Hospital, University of Catania, Catania, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Stagno
authors.affiliation: Chair of Hematology, Department of Biochemistry and Medical Biotechnologies, "Federico II" University, Naples, Italy.
authors.forename: Luigia
authors.initials: L
authors.lastname: Luciano
authors.affiliation: Hematology Unit, "Spedali Civili" Hospital, Brescia, Italy.
authors.forename: Mariella
authors.initials: M
authors.lastname: D'Adda
authors.affiliation: Chair of Hematology, "S.Maria alle Scotte" Hospital, Siena, Italy, University of Siena.
authors.forename: Monica
authors.initials: M
authors.lastname: Bocchia
authors.affiliation: Chair of Hematology, "S. Anna" Hospital, University of Ferrara, Ferrara, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavazzini
authors.affiliation: Chair of Hematology, University of Udine, Udine, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Tiribelli
authors.affiliation: Chair of Hematology, "A. Avogadro" University of Eastern Piedmont, Novara, Italy.
authors.forename: Monia
authors.initials: M
authors.lastname: Lunghi
authors.affiliation: Hematology Unit, IRCCS "Ospedale Casa Sollievo della Sofferenza", S.Giovanni Rotondo, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Pia Falcone
authors.affiliation: Chair of Hematology, University of Messina, Messina, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Musolino
authors.affiliation: Hematology Unit, "Pugliese-Ciaccio" Hospital, Catanzaro, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Levato
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" Hospital, University of Bologna, Bologna, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Venturi
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" Hospital, University of Bologna, Bologna, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Soverini
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" Hospital, University of Bologna, Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
authors.affiliation: Chair of Hematology, "Sapienza" University, Rome, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Alimena
authors.affiliation: Chair of Hematology, Department of Biochemistry and Medical Biotechnologies, "Federico II" University, Naples, 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" Hospital, University of Bologna, Bologna, 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, (Torino), Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" Hospital, University of Bologna, Bologna, Italy.
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
authors.affiliation: Department of Hematology and Oncology "L. and A. Seràgnoli", University of Bologna, Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage* / Q000009:adverse effects; D015466:Leukemia, Myeloid, Chronic-Phase / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib