TY - JOUR
T1 - Long-term results of a phase 2 trial of nilotinib 400 mg twice daily in newly diagnosed patients with chronic-phase chronic myeloid leukemia
AU - Masarova, Lucia
AU - Cortes, Jorge E.
AU - Patel, Keyur P.
AU - O’Brien, Susan
AU - Nogueras-Gonzalez, Graciela M.
AU - Konopleva, Marina
AU - Verstovsek, Srdan
AU - Garcia-Manero, Guillermo
AU - Ferrajoli, Alessandra
AU - Kadia, Tapan M.
AU - Ravandi-Kashani, Farhad
AU - Borthakur, Gautam
AU - DellaSala, Sara
AU - Estrov, Zeev
AU - Jabbour, Elias J.
AU - Kantarjian, Hagop M.
N1 - Publisher Copyright:
© 2020 American Cancer Society
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
KW - chronic myeloid leukemia (CML)
KW - efficacy
KW - frontline
KW - nilotinib
KW - safety
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U2 - 10.1002/cncr.32623
DO - 10.1002/cncr.32623
M3 - Article
C2 - 31999850
AN - SCOPUS:85078838445
SN - 0008-543X
VL - 126
SP - 1448
EP - 1459
JO - Cancer
JF - Cancer
IS - 7
ER -