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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 inhibitors 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 vs. imatinib (ENESTnd). Apart from this registration study, very few data are currently available on nilotinib first-line. We report here the long-term, 6-year, results of the first investigator-sponsored, GIMEMA multicenter phase II, single-arm, trial with nilotinib 400 mg twice daily as first-line treatment in 73 chronic-phase chronic myeloid leukemia patients. Six-year overall survival and progression-free survival 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 nilotinib (400 mg twice daily), highlighting the high efficacy and the cardiovascular toxicity of the drug (CTG.NCT.00481052).

imatinib (ENESTnd). Apart from this registration study, very few data are currently available on nilotinib first-line. We report here the long-term, 6-year, results of the first investigator-sponsored, GIMEMA multicenter phase II, single-arm, trial with nilotinib 400 mg twice daily as first-line treatment in 73 chronic-phase chronic myeloid leukemia patients. Six-year overall survival and progression-free survival 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 nilotinib (400 mg twice daily), highlighting the high efficacy and the cardiovascular toxicity of the drug (CTG.NCT.00481052).
Copyright © 2015, Ferrata Storti Foundation.

http://www.ncbi.nlm.nih.gov/pubmed/26113419