1. Long-term results of a phase 2 trial of nilotinib 400 mg twice daily in newly diagnosed patients with chronic-phase chronic myeloid leukemia.
- Author
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Masarova, Lucia, Cortes, Jorge, Patel, Keyur, OBrien, Susan, Nogueras-Gonzalez, Graciela, Konopleva, Marina, Verstovsek, Srdan, Garcia-Manero, Guillermo, Ferrajoli, Alessandra, Kadia, Tapan, Ravandi-Kashani, Farhad, Borthakur, Gautam, DellaSala, Sara, Estrov, Zeev, Jabbour, Elias, and Kantarjian, Hagop
- Subjects
chronic myeloid leukemia (CML) ,efficacy ,frontline ,nilotinib ,safety ,Adult ,Antineoplastic Agents ,Female ,Humans ,Leukemia ,Myeloid ,Chronic-Phase ,Male ,Middle Aged ,Protein Kinase Inhibitors ,Pyrimidines ,Time ,Treatment Outcome - Abstract
BACKGROUND: Nilotinib is a potent, second-generation inhibitor of BCR-ABL1 tyrosine kinase and has been approved as frontline and salvage therapy for patients with chronic-phase chronic myeloid leukemia (CP-CML). METHODS: In this single-institution, phase 2 study, 122 patients with newly diagnosed CP-CML received nilotinib 400 mg twice daily. The median follow-up on study was 78.3 months (interquartile range, 58.4-96.5 months). RESULTS: Fifty-six percent of patients remained on therapy at the last follow-up. Both the complete cytogenetic response rate and the major molecular response (MR) rate were 91%. Seventy-five percent and 59% of patients achieved a ≥4.5-log reduction in BCR-ABL1 transcripts (MR4.5) and a sustained MR4.5 beyond 2 years, respectively. The estimated event-free survival and overall survival rates at 5 years were 89% and 93%, respectively, and the corresponding rates at 10 years were 85% and 88%, respectively. Treatment discontinuation due to toxicity occurred in 19% of patients, mostly because of cardiovascular events (10%) and biochemical abnormalities (6%). The top 3 nonhematologic toxicities were rash (55%), elevated bilirubin (57%), and elevated aminotransferases (48%). Hematologic toxicity was transient and mild. Ischemic cardiovascular adverse events occurred in 8% of patients. Four patients (3%) progressed to accelerated or blast phase while on therapy, and 7 patients (6%) died on study. CONCLUSIONS: The current data confirm the long-term efficacy of nilotinib 400 mg twice daily in patients with CP-CML. A majority of patients can achieve sustained MR4.5.
- Published
- 2020