Guest guest Posted December 22, 2008 Report Share Posted December 22, 2008 Fostamatinib Disodium Effective for Diffuse B-Cell Lymphoma and CLL Researcher involved in a U.S. multicenter trial have reported that the oral inhibitor of spleen tyrosine kinase (SYK), Fosamatinib disodium (FosD) (R788), has significant activity and is well tolerated in patients with diffuse large B cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL). The results of this phase 1-2 study were reported in the Plenary Session of the 50th annual meeting of the American Society of Hematology on December 7, 2008 in San Francisco.[1] FosD works by disrupting B-cell receptor mediated signaling by inhibiting SYK. This represents a novel approach to the treatment of B cell malignancies. FosD blocks IgG receptor (Fc receptor) signaling in macrophages and B-cells, and addresses multiple inflammatory mechanisms including TNF-?, IL-1, and -6. The agent has shown clinically significant results in treating patients with rheumatoid arthritis.[2] At ASH 2008 researchers from Europe presented data showing that SYK is overexpressed in CLL and represents a potential therapeutic target.[3] This clinical trial included 68 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). Patients in this study had DLCBCL, follicular lymphoma, SLL/CLL, mantle cell lymphoma, marginal zone lymphoma, and MALT. The response rate was 21% for patients with DBCL; this included one complete response, 54% for patients with SLL/CLL, 10% for follicular lymphoma, and 11% for patients with mantle cell lymphoma. Stable disease was observed in 23 patients. FosD was described as well tolerated. These authors stated: " FosD should be developed further, as a single agent and in rational combinations, for BCR-dependent B-cell NHLs. " Comments: FosD appears to be a very novel agent with significant potential for the treatment of B-cell NHL and CLL. References: [1]Friedberg JW, Sharman J, Schaefer-Cutillo J, et al. Fostamatinib disodium (FosD), an oral inhibitior of Syk, is well-tolerated and has significant activity in diffuse large B cell lymphoma (DLBCL) and chronic lymphocytic leukemia. Blood. 2008;112:3, abstract number 3. [2] Weinblatt ME, Kavanaugh A, Bargos-Vargos R, et al. Treatment of rheumatoid arthritis with syk kinase inhibitor: A twelve-week randomized, placebo-controlled trial. Arthritis Rheumatism. 2008;58:3309-3318. [3]Buchner M, Fuchs S, Prinz G, et al. Spleen tyrosine kinase (SYK) is overexpressed and represents a potential therapeutic target in chronic lymphocytic leukemia. Blood. 2008;112:203, abstract number 543. Quote Link to comment Share on other sites More sharing options...
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