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 - Funding Information:
This study was supported in part by Novartis; by the MD Anderson Cancer Center Support Grant CA016672 (principal investigator, Dr. Ronald DePinho), award P01 CA049639 (principal investigator, Dr. Richard Champlin), and the MD Anderson Cancer Center Specialized Program of Research Excellence (SPORE) in Leukemia (grant CA100632) from the National Cancer Institute, National Institutes of Health; the by the Charif Souki Cancer Research Fund.
Funding Information:
This study was supported in part by Bristol‐Myers Squibb; by the MD Anderson Cancer Center Support Grant CA016672 (principal investigator, Dr. Ronald DePinho), award P01 CA049639 (principal investigator, Dr. Richard Champlin), and the MD Anderson Cancer Center Specialized Program of Research Excellence (SPORE) in Leukemia (grant CA100632) from the National Cancer Institute, National Institutes of Health; the by the Charif Souki Cancer Research Fund.
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 -