Kathryn Kolibaba, MD, co-chair, Hematology Research Committee, US Oncology Research, discusses why the Syk inhibitor entospletinib (GS-9973) demonstrates efficacy in patients with mantle cell lymphoma (MCL).

Researchers have known that the Syk tyrosine kinase is active in hematologic malignancies for quite some time, Koliabba explains. The first targeted therapy that was studied in this space was fostamatinib. However, this was not a very specific inhibitor that was associated with high levels of toxicity, as well as high rates of activity on other kinases.

Therefore, researchers were very excited to develop the Syk inhibitor for these patients, in the hopes that there would be strong activity as well as limited levels of toxicity. Results of a phase II trial presented at the 2016 ASH Annual Meeting showed that the therapy was well tolerated and demonstrated modest activity in patients with relapsed or refractory MCL.

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Kathryn Kolibaba, MD, co-chair, Hematology Research Committee, US Oncology Research, discusses why the Syk inhibitor entospletinib demonstrates efficacy in patients with mantle cell lymphoma (MCL).

Dr. Kolibaba on Efficacy of Entospletinib in Mantle Cell Lymphoma

Kathryn Kolibaba, MD, co-chair, Hematology Research Committee, US Oncology Research, discusses the mechanism of action with entospletinib (GS-9973) and its potential as a treatment for patients with mantle cell lymphoma (MCL).

Entospletinib is a specific tyrosine inhibitor directed against (Syk), which is found to be active in many B-cell malignancies. This phase II study explored the agent across several B-cell malignancies, Kolibaba adds. Results of the MCL cohort, in which entospletinib which showed encouraging activity, were presented at the 

Researchers were very excited that a specific inhibitor of Syk was developed in the hopes that there might be efficacy and decreased toxicity. In this study, it was found that the agent was very well tolerated, Kolibaba adds.

Dr. Kolibaba on Mechanism of Action With Entospletinib in MCL

Kathryn Kolibaba, MD, co-chair, Hematology Research Committee, US Oncology Research, discusses a phase II study of entospletinib (GS-9973) in the treatment of patients with mantle cell lymphoma (MCL).

Entospletinib is a selective inhibitor of spleen tyrosine kinase (Syk), which mediates B-cell receptor signaling in normal and transformed B cells. This pathway has been the central focus in several types of B-cell hematologic malignancies, including MCL. In the current study, entospletinib was well tolerated and demonstrated modest activity in patients with relapsed or refractory MCL. These results come from a larger study that broadly assessed the safety and activity of entospletinib in patients with relapsed and refractory hematologic malignancies.

Kolibaba is encouraged by the modest activity and the safety profile demonstrated by entospletinib in this patient cohort, as the agent may have a future role in combination with other drugs in the treatment of patients with MCL.

Kathryn Kolibaba, MD, co-chair, Hematology Research Committee, US Oncology Research, discusses a study of entospletinib in the treatment of patients with mantle cell lymphoma.

Kathryn Kolibaba, MD

Articles

Dr. Kolibaba on Efficacy of Entospletinib in Mantle Cell Lymphoma

Dr. Kolibaba on Mechanism of Action With Entospletinib in MCL

Dr. Kolibaba on Entospletinib Activity in Mantle Cell Lymphoma