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: 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, GIMEMA CML Working Party
• Journal: Haematologica (Haematologica) Vol. 100 Issue 9 Pg. 1146-50 (Sep 2015) ISSN: 1592-8721 [Electronic] Italy
• PMID: 26113419 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Ferrata Storti Foundation.

Chemical References

• Pyrimidines
• Imatinib Mesylate
• nilotinib

Topics

• Adult
• Disease-Free Survival
• Female
• Follow-Up Studies
• Humans
• Imatinib Mesylate (administration & dosage)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, mortality)
• Male
• Pyrimidines (administration & dosage)
• Survival Rate