Abstract
Dasatinib, a potent inhibitor of BCR–ABL in vitro, is effective for patients with chronic myelogenous leukemia (CML) resistant or intolerant to imatinib. To provide a more definitive assessment of dasatinib in chronic-phase (CP)-CML, we report extended follow-up of a phase II trial, presenting data for the entire patient cohort (N=387). Dasatinib (70 mg) twice daily was administered to patients with imatinib-resistant or -intolerant CP-CML. With median follow-up of 15.2 months (treatment duration, <1–18.4 months), a complete hematologic response was attained or maintained in 91% of patients. A major cytogenetic response (MCyR) was attained or maintained by 59% (52% imatinib resistant and 80% imatinib intolerant); this was complete in 49% of patients (40% imatinib resistant and 75% imatinib intolerant). Of 230 patients achieving an MCyR, 7 experienced disease progression. Fifteen-month progression-free survival was 90% while overall survival was 96%. Grade 3/4 thrombocytopenia and neutropenia were reported in 48 and 49% of patients, respectively. Non-hematologic toxicity (any grade) consisted primarily of diarrhea (37%), headache (32%), fatigue (31%), dyspnea (30%) and pleural effusion (27%). Pleural effusions were classified as grade 3 in 6% of reported events, with no incidence of grade 4. Dasatinib is associated with high response rates in patients with imatinib-resistant or -intolerant CP-CML.
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Acknowledgements
In addition to the authors, the following primary investigators also participated in this trial: Australia: C Arthur, S Branford (molecular analyses), A Grigg, J Seymour and K Taylor; Austria: P Valent; Belgium: A Bosly; Canada: D Forrest, C Gambacorti-Passerini and P Laneuville; Denmark: JL Nielsen; Finland: K Porkka; France: J-L Harrousseau, F Maloisel, M Michallet, J Reiffers and P Rousselot; Germany: C Bokemeyer, P Erben (molecular analyses) and T Fischer; Ireland: E Conneally and M O’Dwyer; Israel: A Nagler; Italy: E Abruzzese, F Castagnetti, F Ferrara, G Lambertenghi, V Liso, G Rosti, B Rotoli and G Saglio; Korea: D-W Kim; Netherlands: J Cornelissen and AVMB Schattenberg; Peru: J Navarro; Singapore: YT Goh; Spain: J Odriozola and JL Steegmann; Sweden: M Ekblom, B Markevarn, B Simonsson and L Stenke; Switzerland: A Gratwohl; UK: T Holyoake; USA: K Bhalla, S Bilgrami, B Cheson, R Collins, S Coutre, J Dipersio, S Durham, L Fehrenbacher, JK Giguere, FA Greco, HJ Khoury, M Lilly, J Lister, S Luger, A Maniam, J McGuirk, E Merriam, MS Murali, J Radich (molecular analyses), A Rapoport, CE Rivera, C Schiffer, R Strair and M Talpaz. Professional writing and editorial assistance, funded by Bristol–Myers Squibb, was provided by Josh Collis and Andrew Richardson. The funding for this trial was provided by Bristol–Myers Squibb.
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This trial (trial no. CA180-013) is registered at http://www.clinicaltrials.gov.
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Hochhaus, A., Baccarani, M., Deininger, M. et al. Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. Leukemia 22, 1200–1206 (2008). https://doi.org/10.1038/leu.2008.84
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DOI: https://doi.org/10.1038/leu.2008.84
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