By Nandita Khera, MD, of the Fred Hutchinson Cancer Research Center, and Bart Scott, MD
2008-12-08
Yesterday at the Plenary Session, Dr. Jonathan W. Friedberg and colleagues presented data about fostamatinib disodium (FosD), a new drug in the arena of novel therapeutic agents that are known to act by modulating B-cell signaling pathways (abstract #3). FosD is an oral inhibitor of spleen tyrosine kinase (Syk) that has shown clinical benefit in patients with rheumatoid arthritis. In mouse models of NHL, it has shown efficacy by inducing apoptosis in transformed B cells in vitro and causing tumor regression in vivo.
The authors reported results of the first clinical trial of FosD in patients with relapsed or refractory NHL. Phase I of the study included 13 patients with follicular lymphoma (FL), chronic lymphocytic leukemia/small cell lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL), and defined the optimum treatment dose for phase II as 200 mg BID. Sixty-eight patients with relapsed or refractory NHL who had been heavily pretreated (median of 5 prior therapies) were enrolled in the phase II stage. The investigators reported favorable outcomes across all three separate disease cohorts (DLBCL, FL, and other B-cell lymphomas including SLL/CLL, mantle cell, marginal zone, and lymphoplasmacytic lymphoma). Response rates ranged from 10 percent in FL to 54 percent in SLL/CLL and 21 percent in DLBCL with a median PFS of 4.5 months. There were four deaths due to disease progression and one death secondary to infection following therapy. The investigators concluded that it is a safe and well-tolerated approach to relapsed or refractory lymphoma.
Modulating the B-cell signaling pathway offers a novel therapeutic approach in B-cell malignancies. More studies including randomized trials of this drug are needed to further elucidate its potential in relapsed or refractory NHLs as a single agent or in combination with other chemotherapeutic agents. For now we are content in knowing that a novel therapeutic target is under active investigation for patients with B-cell-derived malignancies.
Drs. Khera and Scott indicated no relevant conflicts of interest.
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