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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2309-2315.
Prepublished online as a Blood First Edition Paper on May 11, 2007; DOI 10.1182/blood-2007-02-073528.
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CLINICAL TRIALS AND OBSERVATIONS
Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study
Oliver Ottmann1,
Hervé Dombret2,
Giovanni Martinelli3,
Bengt Simonsson4,
Francois Guilhot5,
Richard A. Larson6,
Giovanna Rege-Cambrin7,
Jerald Radich8,
Andreas Hochhaus9,
Anne Marie Apanovitch10,
Ashwin Gollerkeri11, and
Steven Coutre12
1 Medizinische Klinik II, Johann Wolfgang Goethe Universität, Frankfurt, Germany;
2 Hospital Saint Louis, Paris Cedex, France;
3 Istituto di Ematologica E Oncologica Medica, Policlinico S Orsola, Bologna, Italy;
4 Department of Hematology, University Hospital, Uppsala, Sweden;
5 Clinical Research Centre, Centre Hospitalier Universitaire la Milétrie, Poitiers, France;
6 University of Chicago, IL;
7 Dipartimento di Medicina Interna ii ed Ematologia, Azienda Ospedaliera S. Luigi, Orbassano, Italy;
8 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
9 Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany;
10 Bristol-Myers Squibb, Hopewell, NJ;
11 Bristol-Myers Squibb, Wallingford, CT; and
12 Stanford University School of Medicine, CA
Patients with Philadelphia (Ph) chromosome–positive acute lymphoblastic leukemia (ALL) have a rapid disease course and a poor prognosis. Dasatinib, a novel, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, has previously induced responses in patients with imatinib-resistant or -intolerant Ph-positive ALL. We present the interim results of a phase 2 study designed to further assess the efficacy, safety, and tolerability of dasatinib 140 mg in this patient population (n = 36). With a minimum follow-up of 8 months, treatment with dasatinib resulted in substantial hematologic and cytogenetic response rates. Major hematologic responses were achieved in 42% (15/36) of patients, 67% of whom remained progression-free. Complete cytogenetic responses were attained by 58% (21/36) of patients. The presence of BCR-ABL mutations conferring imatinib resistance did not preclude a response to dasatinib. Dasatinib was also tolerable, with 6% (2/36) of patients discontinuing therapy as a result of study-drug toxicity. Most adverse events (AEs) were grade 1 or 2; febrile neutropenia was the most frequent severe AE, but this and other cytopenias were manageable with dose reduction. Dasatinib represents a safe and effective treatment option and an important therapeutic advance for patients with Ph-positive ALL. This trial was registered at www.clinicaltrials.gov as #CA180015.
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