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Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib

¹ Division of Hematology and Oncology, University of California, San Francisco School of Medicine, San Francisco, CA, USA
² Division of Hematology, St Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea
³ MD Anderson Cancer Center, Houston, TX, USA
⁴ Hôpital Mignot and CIC Hôpital Saint Louis, Paris, France
⁵ Hospital das Clinicas, Sao Paulo, Brazil
⁶ Instituto de Trasplante de Medula Osea, La Plata, Argentina
⁷ Centro Medico Nacional La Raza IMSS, Mexico
⁸ Division of Hematology/Oncology, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, USA
⁹ Dept. of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
¹⁰ III Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany
¹¹ Bristol-Myers Squibb, Wallingford, CT, USA
¹² Dept. of Hematology/Oncology, Universitätsklinikum Jena, Jena, Germany

Correspondence: Neil P. Shah, MD, UCSF-Hematology/Oncology, Suite M1286, Box 1270, 505 Parnassus Ave, San Francisco, CA 94143, USA. E-mail: nshah{at}medicine.ucsf.edu

Background: Dasatinib 100 mg once daily achieves intermittent BCR-ABL kinase inhibition and is approved for chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib. To better assess durability of response to and tolerability of dasatinib, data from a 2-year minimum follow-up for a dose-optimization study in chronic-phase chronic myeloid leukemia are reported here.

Design and Methods: In a phase 3 study, 670 chronic-phase chronic myeloid leukemia patients with resistance, intolerance, or suboptimal response to imatinib were randomized to dasatinib 100 mg once-daily, 50 mg twice-daily, 140 mg once-daily, or 70 mg twice-daily.

Results: Data from a 2-year minimum follow-up demonstrate that dasatinib 100 mg once daily achieves major cytogenetic response and complete cytogenetic response rates comparable to those in the other treatment arms, and reduces the frequency of key side effects. Comparable 2-year progression-free survival and overall survival rates were observed (80% and 91%, respectively, for 100 mg once daily, and 75%–76% and 88%–94%, respectively, in other arms). Complete cytogenetic responses were achieved rapidly, typically by 6 months. In patients treated with dasatinib 100 mg once daily for 6 months without complete cytogenetic response, the likelihood of achieving such a response by 2 years was 50% for patients who had achieved a partial cytogenetic response, and only 8% or less for patients with minor, minimal, or no cytogenetic response. Less than 3% of patients suffered disease transformation to accelerated or blast phase.

Conclusions: Intermittent kinase inhibition can achieve rapid and durable responses, indistinguishable from those achieved with more continuous inhibition.

Key words: chronic myeloid leukemia, chronic phase, dasatinib, cytogenetic response, inhibition.