Fostamatinib Disodium Effective for Diffuse B-Cell Lymphoma and CLL

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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.