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Oncotarget. 2018 Feb 12;9(18):14219-14227. doi: 10.18632/oncotarget.24478. eCollection 2018 Mar 6.

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

Author information

1
Division of Hematology and Bone Marrow Transplantation, Department of Medical Area, ASUI Udine, Udine, Italy.
2
Department of Medicine, Section of Hematology, University of Verona, Verona, Italy.
3
Department of Medicine, Hematology Section, Padua University School of Medicine, Padua, Italy.
4
Hematology Division, IRCCS Ca' Granda-Maggiore Policlinico Hospital Foundation, Milan, Italy.
5
Hematology Unit, Ca' Foncello Hospital, Treviso, Italy.
6
Hematology Unit, Dell'Angelo Hospital, Venezia-Mestre, Italy.
7
Hematology Unit, Santa Chiara Hospital, Trento, Italy.
8
Division of Clinical Hematology, AOU Ospedali Riuniti, Trieste, Italy.
9
Department of Medical Specialities, Oncology and Onco-Hematology Unit, Venice, Italy.
10
Hematology Unit, P. Cosma Hospital, Camposampiero, Padua, Italy.
#
Contributed equally

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.

KEYWORDS:

CML; dasatinib; nilotinib; outcomes; second-line

Conflict of interest statement

CONFLICTS OF INTEREST M. Tiribelli, M. Bonifacio and G. Binotto have received speaker bureau and advisory board honorarium from Novartis, Bristol-Myers Squibb (BMS), Pfizer and Incyte, outside the present study. A. Iurlo have received speaker bureau from Novartis, Bristol-Myers Squibb (BMS), Pfizer and Incyte, outside the present study. All other authors declare no competing financial interests.

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