Long-term results of frontline dasatinib in chronic myeloid leukemia

Abhishek Maiti, Jorge E. Cortes, Keyur P. Patel, Lucia Masarova, Gautam Borthakur, Farhad Ravandi, Srdan Verstovsek, Alessandra Ferrajoli, Zeev Estrov, Guillermo Garcia-Manero, Tapan M. Kadia, Graciela M. Nogueras-González, Jeffrey Skinner, Rebecca Poku, Sara DellaSala, Rajyalakshmi Luthra, Elias J. Jabbour, Susan O’Brien, Hagop M. Kantarjian

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1502-1511
Number of pages10
JournalCancer
Volume126
Issue number7
DOIs
StatePublished - Apr 1 2020
Externally publishedYes

Keywords

  • chromic myeloid leukemia
  • dasatinib
  • early chronic phase
  • frontline

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Long-term results of frontline dasatinib in chronic myeloid leukemia'. Together they form a unique fingerprint.

  • Cite this

    Maiti, A., Cortes, J. E., Patel, K. P., Masarova, L., Borthakur, G., Ravandi, F., Verstovsek, S., Ferrajoli, A., Estrov, Z., Garcia-Manero, G., Kadia, T. M., Nogueras-González, G. M., Skinner, J., Poku, R., DellaSala, S., Luthra, R., Jabbour, E. J., O’Brien, S., & Kantarjian, H. M. (2020). Long-term results of frontline dasatinib in chronic myeloid leukemia. Cancer, 126(7), 1502-1511. https://doi.org/10.1002/cncr.32627