Long-term outcome of a phase 2 trial with nilotinib 400 mg twice daily in first-line treatment of chronic myeloid leukemia
Gabriele Gugliotta,
Fausto Castagnetti,
Massimo Breccia,
Luciano Levato,
Mariella D’Adda,
Fabio Stagno,
Mario Tiribelli,
Marzia Salvucci,
Carmen Fava,
Bruno Martino,
Michele Cedrone,
Monica Bocchia,
Elena Trabacchi,
Francesco Cavazzini,
Emilio Usala,
Antonella Russo Rossi,
Maria Teresa Bochicchio,
Simona Soverini,
Giuliana Alimena,
Michele Cavo,
Fabrizio Pane,
Giovanni Martinelli,
Giuseppe Saglio,
Michele Baccarani,
Gianantonio Rosti
Affiliations
Gabriele Gugliotta
Institute of Hematology “L. and A. Seràgnoli”, Department of Experimental, Diagnostic and Specialty Medicine, “S. Orsola-Malpighi” University Hospital, University of Bologna, Roma, Italy
Fausto Castagnetti
Institute of Hematology “L. and A. Seràgnoli”, Department of Experimental, Diagnostic and Specialty Medicine, “S. Orsola-Malpighi” University Hospital, University of Bologna, Roma, Italy
Massimo Breccia
Chair of Hematology, “Sapienza” University, Roma, Italy
Luciano Levato
Hematology Unit, “Pugliese-Ciaccio” Hospital, Catanzaro, Italy
Mariella D’Adda
Hematology Unit, “Spedali Civili” Hospital, Brescia, Ravenna, Italy
Fabio Stagno
Chair of Hematology, University of Catania, Ravenna, Italy
Mario Tiribelli
Chair of Hematology, University of Udine, Ravenna, Italy
Marzia Salvucci
Hematology Unit, “S. Maria delle Croci” Hospital, Ravenna, Italy
Carmen Fava
Chair of Hematology, Department of Clinical and Biological Sciences, “S. Luigi Gonzaga” University Hospital, University of Torino, Orbassano, Italy
Bruno Martino
Hematology Unit, “Bianchi-Melacrino-Morelli” Hospital, Reggio Calabria, Italy
Michele Cedrone
Hematology Unit, “S. Giovanni Addolorata” Hospital, Roma, Italy
Monica Bocchia
Chair of Hematology, “S. Maria alle Scotte” Hospital, University of Siena, Piacenza, Italy
Elena Trabacchi
Hematology Unit, “Guglielmo da Saliceto” Hospital, Piacenza, Italy
Francesco Cavazzini
Chair of Hematology, “S. Anna” University Hospital, University of Ferrara, Cagliari, Italy
Emilio Usala
Hematology Unit, “A. Businco” Hospital, Cagliari, Italy
Antonella Russo Rossi
Chair of Hematology, University of Bari, Napoli, Italy
Maria Teresa Bochicchio
Institute of Hematology “L. and A. Seràgnoli”, Department of Experimental, Diagnostic and Specialty Medicine, “S. Orsola-Malpighi” University Hospital, University of Bologna, Roma, Italy
Simona Soverini
Institute of Hematology “L. and A. Seràgnoli”, Department of Experimental, Diagnostic and Specialty Medicine, “S. Orsola-Malpighi” University Hospital, University of Bologna, Roma, Italy
Giuliana Alimena
Chair of Hematology, “Sapienza” University, Roma, Italy
Michele Cavo
Institute of Hematology “L. and A. Seràgnoli”, Department of Experimental, Diagnostic and Specialty Medicine, “S. Orsola-Malpighi” University Hospital, University of Bologna, Roma, Italy
Fabrizio Pane
Chair of Hematology, Department of Biochemistry and Medical Biotechnologies, “Federico II” University, Napoli, Italy
Giovanni Martinelli
Institute of Hematology “L. and A. Seràgnoli”, Department of Experimental, Diagnostic and Specialty Medicine, “S. Orsola-Malpighi” University Hospital, University of Bologna, Roma, Italy
Giuseppe Saglio
Chair of Hematology, Department of Clinical and Biological Sciences, “S. Luigi Gonzaga” University Hospital, University of Torino, Orbassano, Italy
Michele Baccarani
Department of Hematology and Oncology “L. and A. Seràgnoli”, University of Bologna, Italy
Gianantonio Rosti
Institute of Hematology “L. and A. Seràgnoli”, Department of Experimental, Diagnostic and Specialty Medicine, “S. Orsola-Malpighi” University Hospital, University of Bologna, Roma, Italy
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).