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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(s) -
Masarova Lucia,
Cortes Jorge E.,
Patel Keyur P.,
O’Brien Susan,
NoguerasGonzalez Graciela M.,
Konopleva Marina,
Verstovsek Srdan,
GarciaManero Guillermo,
Ferrajoli Alessandra,
Kadia Tapan M.,
RavandiKashani Farhad,
Borthakur Gautam,
DellaSala Sara,
Estrov Zeev,
Jabbour Elias J.,
Kantarjian Hagop M.
Publication year - 2020
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.32623
Subject(s) - medicine , nilotinib , discontinuation , myeloid leukemia , interquartile range , adverse effect , rash , gastroenterology , imatinib mesylate , imatinib , surgery
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.