Excellent outcomes of 2G-TKI therapy after imatinib failure in chronic phase CML patients

Mario Tiribelli, Massimiliano Bonifacio, Gianni Binotto, Alessandra Iurlo, Francesca Cibien, Elena Maino, Anna Guella, Gianluca Festini, Claudia Minotto, Ercole De Biasi, Federico De Marchi, Luigi Scaffidi, Luca Frison, Cristina Bucelli, Marta Medeot, Elisabetta Calistri, Rosaria Sancetta, Manuela Stulle, Nicola Orofino, Mauro KramperaFilippo Gherlinzoni, Gianpietro Semenzato, Giovanni Pizzolo, Achille Ambrosetti, Renato Fanin

Research output: Contribution to journalArticle

Abstract

Second-generation tyrosine kinase inhibitors (2G-TKIs) dasatinib and nilotinib produced historical rates of about 50% complete cytogenetic response (CCyR) and about 40% major molecular response (MMR) in chronic myeloid leukaemia (CML) patients failing imatinib. Direct comparisons between dasatinib and nilotinib are lacking, and few studies addressed the dynamics of deep molecular response (DMR) in a "real-life" setting. We retrospectively analyzed 163 patients receiving dasatinib (n = 95) or nilotinib (n = 68) as second-line therapy after imatinib. The two cohorts were comparable for disease's characteristics, although there was a higher rate of dasatinib use in imatinib-resistant and of nilotinib in intolerant patients. Overall, 75% patients not in CCyR and 60% patients not in MMR at 2G-TKI start attained this response. DMR was achieved by 61 patients (37.4%), with estimated rate of stable DMR at 5 years of 24%. After a median follow-up of 48 months, 60% of patients persisted on their second-line treatment. Rates and kinetics of cytogenetic and molecular responses, progression-free and overall survival were similar for dasatinib and nilotinib. In a "real-life" setting, dasatinib and nilotinib resulted equally effective and safe after imatinib failure, determining high rates of CCyR and MMR, and a significant chance of stable DMR, a prerequisite for treatment discontinuation.

Original languageEnglish
Pages (from-to)14219-14227
Number of pages9
JournalOncotarget
Volume9
Issue number18
DOIs
Publication statusPublished - Jan 1 2018

Keywords

  • CML
  • Dasatinib
  • Nilotinib
  • Outcomes
  • Second-line

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Tiribelli, M., Bonifacio, M., Binotto, G., Iurlo, A., Cibien, F., Maino, E., Guella, A., Festini, G., Minotto, C., De Biasi, E., De Marchi, F., Scaffidi, L., Frison, L., Bucelli, C., Medeot, M., Calistri, E., Sancetta, R., Stulle, M., Orofino, N., ... Fanin, R. (2018). Excellent outcomes of 2G-TKI therapy after imatinib failure in chronic phase CML patients. Oncotarget, 9(18), 14219-14227. https://doi.org/10.18632/oncotarget.24478