Oncotarget

Research Papers:

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 Krampera, Filippo Gherlinzoni, Gianpietro Semenzato, Giovanni Pizzolo, Achille Ambrosetti and Renato Fanin

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Oncotarget. 2018; 9:14219-14227. https://doi.org/10.18632/oncotarget.24478

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Abstract

Mario Tiribelli1,*, Massimiliano Bonifacio2,*, Gianni Binotto3, Alessandra Iurlo4, Francesca Cibien5, Elena Maino6, Anna Guella7, Gianluca Festini8, Claudia Minotto9, Ercole De Biasi10, Federico De Marchi1, Luigi Scaffidi2, Luca Frison3, Cristina Bucelli4, Marta Medeot1, Elisabetta Calistri5, Rosaria Sancetta6, Manuela Stulle8, Nicola Orofino4, Mauro Krampera2, Filippo Gherlinzoni5, Gianpietro Semenzato3, Giovanni Pizzolo2, Achille Ambrosetti2 Renato Fanin1

1Division of Hematology and Bone Marrow Transplantation, Department of Medical Area, ASUI Udine, Udine, Italy

2Department of Medicine, Section of Hematology, University of Verona, Verona, Italy

3Department of Medicine, Hematology Section, Padua University School of Medicine, Padua, Italy

4Hematology Division, IRCCS Ca’ Granda–Maggiore Policlinico Hospital Foundation, Milan, Italy

5Hematology Unit, Ca’ Foncello Hospital, Treviso, Italy

6Hematology Unit, Dell'Angelo Hospital, Venezia-Mestre, Italy

7Hematology Unit, Santa Chiara Hospital, Trento, Italy

8Division of Clinical Hematology, AOU Ospedali Riuniti, Trieste, Italy

9Department of Medical Specialities, Oncology and Onco-Hematology Unit, Venice, Italy

10Hematology Unit, P. Cosma Hospital, Camposampiero, Padua, Italy

*These authors contributed equally to this work

Correspondence to:

Mario Tiribelli, email: [email protected]

Keywords: CML; dasatinib; nilotinib; second-line; outcomes

Received: December 05, 2017     Accepted: January 30, 2018     Epub: February 12, 2018     Published: March 06, 2018

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.


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