TY - JOUR
T1 - Long-term results of frontline dasatinib in chronic myeloid leukemia
AU - Maiti, Abhishek
AU - Cortes, Jorge E.
AU - Patel, Keyur P.
AU - Masarova, Lucia
AU - Borthakur, Gautam
AU - Ravandi, Farhad
AU - Verstovsek, Srdan
AU - Ferrajoli, Alessandra
AU - Estrov, Zeev
AU - Garcia-Manero, Guillermo
AU - Kadia, Tapan M.
AU - Nogueras-González, Graciela M.
AU - Skinner, Jeffrey
AU - Poku, Rebecca
AU - DellaSala, Sara
AU - Luthra, Rajyalakshmi
AU - Jabbour, Elias J.
AU - O’Brien, Susan
AU - Kantarjian, Hagop M.
N1 - Funding Information:
This study was supported in part by Bristol‐Myers Squibb, and by the MD Anderson Cancer Center Support Grant CA016672 (principal investigator, Dr. Ronald DePinho) and award P01 CA049639 (principal investigator, Dr. Richard Champlin) from the National Cancer Institute, National Institutes of Health.
Funding Information:
This study was supported in part by Bristol-Myers Squibb, and by the MD Anderson Cancer Center Support Grant CA016672 (principal investigator, Dr. Ronald DePinho) and award P01 CA049639 (principal investigator, Dr. Richard Champlin) from the National Cancer Institute, National Institutes of Health. Abhishek Maiti reports research funding from Celgene outside the submitted work. Jorge E. Cortes reports research funding from Ambit BioSciences, ARIAD, Arog, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Celator, Celgene, Novartis, Pfizer, Sanofi, Sun Pharma, and Teva; and personal fees from Ambit BioSciences, ARIAD, Astellas Pharma, BiolineRx, Bristol-Myers Squibb, Novartis, and Pfizer, all outside the submitted work. Farhad Ravandi reports research funding from Amgen, Bristol-Myers Squibb, Merck, Seattle Genetics, and Sunesis Pharmaceuticals; honoraria from Amgen, Pfizer, Seattle Genetics, and Sunesis Pharmaceuticals; and personal fees from Amgen, Seattle Genetics, Agios, AbbVie, Astellas, Daichii, and Sunesis Pharmaceuticals, all outside the submitted work. Tapan M. Kadia: reports personal fees from Novartis and research funding from Bristol-Myers Squibb outside the submitted work. Elias J. Jabbour reports research funding from Bristol-Myers Squibb, Takeda, Novartis, and Pfizer outside the submitted work. Susan O?Brien reports personal fees from Amgen, Astellas, Celgene, GlaxoSmithKline, Janssen Oncology, Aptose Biosciences Inc, Vaniam Group LLC, AbbVie, Alexion, Verastem, and Eisai; research support from Kite, Regeneron, and Acerta; and personal fees and research support from Gilead, Pharmacyclics, TG Therapeutics, Pfizer, and Sunesis Pharmaceuticals, all outside the submitted work. Hagop M. Kantarjian reports grants from AbbVie, Agios, Amgen, ARIAD, Astex, Bristol-Myers Squibb, Cyclacel, Daichii-Sanko, Delta-Fly Pharma, Immunogen, Jazz Pharma, Novartis, and Pfizer; honoraria from AbbVie, Agios, Amgen, Immunogen, Pfizer, and Takeda; and personal fees from Actinium, all outside the submitted work. The remaining authors made no disclosures.
Publisher Copyright:
© 2020 American Cancer Society
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Background: Dasatinib is a second-generation tyrosine kinase inhibitor that, when used as frontline therapy, produces more and faster cytogenetic and molecular responses compared with imatinib. The authors report the long-term follow-up from the first study using dasatinib as initial therapy for chronic-phase chronic myeloid leukemia. Methods: Between November 2005 and August 2014, patients were randomly assigned to receive 100 mg daily or 50 mg twice daily. After June 2009, all patients started with 100 mg daily. Results: With a median follow-up of 6.5 years, 94 of 149 treated patients (63%) were still receiving dasatinib on study. The median patient age was 48 years (interquartile range, 37-55 years), and 9% of patients had a high risk Sokal risk score. The cumulative complete cytogenetic response rate at 11 years was 92.6%, the major molecular response (MR) rate was 88.2%, and the MR4.5 rate (indicating a ≥4.5-log reduction in BCR-ABL1 transcripts) was 79.5%. The median time to a major MR and MR4.5 was 6 and 23 months, respectively. A sustained MR4.5 (≥2 years) was achieved in 82 patients (55%). The 10-year overall survival, transformation-free survival, event-free survival, and failure-free survival rates were 89%, 95%, 86%, and 65%, respectively. Univariate analysis showed that the achievement of a complete MR was associated with improved overall survival. The most common reasons for treatment discontinuation were toxicity and elective discontinuation. The most common treatment-emergent grade 3 and 4 adverse events were fatigue, thrombocytopenia, and infections. Conclusions: After this long-term follow-up, dasatinib continues to show an excellent safety profile and produces rapid cytogenetic responses and MRs, durable deep MRs, and excellent long-term survival outcomes in patients with chronic-phase chronic myeloid leukemia.
AB - Background: Dasatinib is a second-generation tyrosine kinase inhibitor that, when used as frontline therapy, produces more and faster cytogenetic and molecular responses compared with imatinib. The authors report the long-term follow-up from the first study using dasatinib as initial therapy for chronic-phase chronic myeloid leukemia. Methods: Between November 2005 and August 2014, patients were randomly assigned to receive 100 mg daily or 50 mg twice daily. After June 2009, all patients started with 100 mg daily. Results: With a median follow-up of 6.5 years, 94 of 149 treated patients (63%) were still receiving dasatinib on study. The median patient age was 48 years (interquartile range, 37-55 years), and 9% of patients had a high risk Sokal risk score. The cumulative complete cytogenetic response rate at 11 years was 92.6%, the major molecular response (MR) rate was 88.2%, and the MR4.5 rate (indicating a ≥4.5-log reduction in BCR-ABL1 transcripts) was 79.5%. The median time to a major MR and MR4.5 was 6 and 23 months, respectively. A sustained MR4.5 (≥2 years) was achieved in 82 patients (55%). The 10-year overall survival, transformation-free survival, event-free survival, and failure-free survival rates were 89%, 95%, 86%, and 65%, respectively. Univariate analysis showed that the achievement of a complete MR was associated with improved overall survival. The most common reasons for treatment discontinuation were toxicity and elective discontinuation. The most common treatment-emergent grade 3 and 4 adverse events were fatigue, thrombocytopenia, and infections. Conclusions: After this long-term follow-up, dasatinib continues to show an excellent safety profile and produces rapid cytogenetic responses and MRs, durable deep MRs, and excellent long-term survival outcomes in patients with chronic-phase chronic myeloid leukemia.
KW - chromic myeloid leukemia
KW - dasatinib
KW - early chronic phase
KW - frontline
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U2 - 10.1002/cncr.32627
DO - 10.1002/cncr.32627
M3 - Article
C2 - 31999839
AN - SCOPUS:85078918859
SN - 0008-543X
VL - 126
SP - 1502
EP - 1511
JO - Cancer
JF - Cancer
IS - 7
ER -