An open-label clinical trial for non-Hodgkin B-cell lymphoma tested fostamatinib tablets in 81 patients with a lymphoid malignancy. Results indicate that fostamatinib has some level of efficacy in patients with diffuse large B-cell lymphoma (DLBCL), as well as patients with mantle cell lymphoma, mucosa-associated lymphoid tissue lymphoma, marginal zone lymphomas, small lymphocyctic lymphomas and chronic lymphocytic leukemia (other lymphomas).
“Efficacy and Safety Study of Fostamatinib Tablets to Treat B-cell Lymphoma,” sponsored by AstraZeneca, consisted of a Phase 1 and a Phase 2 study. Thirteen patients were enrolled in Phase 1 and 68 patients were enrolled in Phase 2, though only Phase 2 data was provided as the primary outcome measures were not tested in Phase 1 patients. These outcomes included overall response rate, clinical benefit rate, progression free survival, and overall survival. Treatment lasted for a maximum of 511 days and consisted of one of two doses of fostamatinib tablets orally twice a day.
According to the study results, two of the 21 patients with DLBCL treated with fostamatinib demonstrated a response to treatment. Responses were assessed according to the Revised Response Criteria for Malignant Lymphomas and described patients achieving a complete response or a partial response. Seven of the 24 patients with other lymphomas achieved a response. Looking at clinical benefit rate, which was a more analytical technique that identified response in tumor samples, 13 of the 21 patients treated with fostamatinib and 14 of the 24 with other lymphomas showed a response, respectively.
Previously, scientists at a variety of medical centers and universities across the nation and researchers at Rigel Pharmaceuticals studied fostamatinib in patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia. The team identified one of fostamatinib’s mechanism of action in the treatment of lymphoma. The drug inhibits spleen tyrosine kinase (Syk), a protein that is integral in initiating and amplifying the B-cell receptor-mediated survival signal. In the case of lymphoma, this survival signal allows tumor cells to divide and multiply. By inhibiting the signal, fostamatinib causes lymphoma cells to apoptose. The study was published in the journal Blood and is entitled, “Inhibition of Syk with Fostamatinib Disodium Has Significant Activity in Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia.”
Rigel Pharmaceuticals is currently enrolling two Phase 3 clinical trials for fostamatinib in a blood disorder known as immune thrombocytopenic purpura (ITP). Clinical trials such as these will continue to add to the body of knowledge of how fostamatinib acts as an inhibitor of B-cells, further elucidating the mechanism of action in disease.