锡克
慢性淋巴细胞白血病
医学
套细胞淋巴瘤
滤泡性淋巴瘤
癌症研究
内科学
淋巴瘤
氯霉素
伊布替尼
肿瘤科
白血病
伊德里希
免疫学
CD20
酪氨酸激酶
受体
作者
Jonathan W. Friedberg,Jeff P. Sharman,John Sweetenham,Patrick B. Johnston,Julie M. Vose,Ann S. LaCasce,Julia Schaefer-Cutillo,Sven de Vos,Rajni Sinha,John P. Leonard,Larry D. Cripe,Stephanie A. Gregory,Michael Sterba,Ann Lowe,Ronald Levy,Margaret A. Shipp
出处
期刊:Blood
[American Society of Hematology]
日期:2010-04-01
卷期号:115 (13): 2578-2585
被引量:678
标识
DOI:10.1182/blood-2009-08-236471
摘要
Abstract Certain malignant B cells rely on B-cell receptor (BCR)–mediated survival signals. Spleen tyrosine kinase (Syk) initiates and amplifies the BCR signal. In in vivo analyses of B-cell lymphoma cell lines and primary tumors, Syk inhibition induces apoptosis. These data prompted a phase 1/2 clinical trial of fostamatinib disodium, the first clinically available oral Syk inhibitor, in patients with recurrent B-cell non-Hodgkin lymphoma (B-NHL). Dose-limiting toxicity in the phase 1 portion was neutropenia, diarrhea, and thrombocytopenia, and 200 mg twice daily was chosen for phase 2 testing. Sixty-eight patients with recurrent B-NHL were then enrolled in 3 cohorts: (1) diffuse large B-cell lymphoma (DLBCL), (2) follicular lymphoma (FL), and (3) other NHL, including mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), mucosa-associated lymphoid tissue lymphoma, lymphoplasmacytic lymphomas, and small lymphocytic leukemia/chronic lymphocytic leukemia (SLL/CLL). Common toxicities included diarrhea, fatigue, cytopenias, hypertension, and nausea. Objective response rates were 22% (5 of 23) for DLBCL, 10% (2 of 21) for FL, 55% (6 of 11) for SLL/CLL, and 11% (1/9) for MCL. Median progression-free survival was 4.2 months. Disrupting BCR-induced signaling by inhibiting Syk represents a novel and active therapeutic approach for NHL and SLL/CLL. This trial was registered at www.clinicaltrials.gov as #NCT00446095.
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