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

被引:276
作者
Ottmann, Oliver
Dombret, Herve
Martinelli, Giovanni
Simonsson, Bengt
Guilhot, Francois
Larson, Richard A.
Rege-Cambrin, Giovanna
Radich, Jerald
Hochhaus, Andreas
Apanovitch, Anne Marie
Gollerkeri, Ashwin
Coutre, Steven
机构
[1] Goethe Univ Frankfurt, Med Klin 2, Abt Haematol, D-60590 Frankfurt, Germany
[2] Hosp St Louis, Paris, France
[3] Policlin S Orsola, Ist Ematol Oncol Med E, Bologna, Italy
[4] Univ Uppsala Hosp, Dept Hematol, Uppsala, Sweden
[5] CHU La Miletrie, Clin Res Ctr, Poitiers, France
[6] Univ Chicago, Chicago, IL 60637 USA
[7] Azienda Osped S Luigi, Dipartimento Med Interna & Ematol, Orbassano, Italy
[8] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA
[9] Univ Heidelberg, Med Fak Mannheim, D-6800 Mannheim, Germany
[10] Bristol Myers Squibb Co, Hopewell, NJ USA
[11] Bristol Myers Squibb Co, Wallingford, CT 06492 USA
[12] Stanford Univ, Sch Med, Stanford, CA 94305 USA
关键词
D O I
10.1182/blood-2007-02-073528
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 indatinib-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.
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页码:2309 / 2315
页数:7
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