Single Agent Entospletinib Induces Modest Activity in Lymphoma Subgroups

November 13, 2018

Entospletinib monotherapy yielded limited activity in patients with relapsed or refractory indolent non-Hodgkin lymphoma and mantle cell lymphoma.

Entospletinib monotherapy yielded limited activity in patients with relapsed or refractory indolent non-Hodgkin lymphoma and mantle cell lymphoma, according to phase 2 study results published in the British Journal of Haematology.

“There remains a significant unmet need with regard to the treatment of relapsed/refractory indolent non-Hodgkin lymphoma and mantle cell lymphoma,” the researchers wrote. “…mantle cell lymphoma is a rare subtype of non-Hodgkin lymphoma with an aggressive clinical course that usually responds to first-line chemotherapy but remains incurable with an overall poor prognosis.”

In an open-label, multicenter phase 2 trial, researchers enrolled patients with various blood cancers to determine the safety, tolerability and efficacy of single agent entospletinib at a dose of 800 mg twice daily.

While the overall study included five cancer types, the researchers reported on those with follicular lymphoma (41 patients), lymphoplasmacytic lymphoma/Waldenstroem macroglobulinaemia (17 patients), marginal zone lymphoma (17 patients) and mantle cell lymphoma (39 patients).

Progression-free survival — or the time until disease progression or worsening – at 16 weeks for patients with mantle cell lymphoma and at 24 weeks for patients with indolent non-Hodgkin lymphoma served as the primary endpoint of the study.

The majority of patients were male (58.8 percent), a median age of 71 years and received a median of three prior therapies.

Progression-free survival at 16 weeks in the mantle cell lymphoma group was 63.9 percent. At 24 weeks, progression free survival was 51.5 percent in those with follicular lymphoma, 69.8 percent in patients with lymphoplasmacytic lymphoma/Waldenstroem macroglobulinaemia, 56.6 percent in those with mantle cell lymphoma and 46.2 percent in patients with marginal zone lymphoma.

In addition, the researchers noted activity with entospletinib as a single agent was modest, with overall response rates of 17.1 percent in those with follicular lymphoma, 35.3 percent in patients lymphoplasmacytic lymphoma/Waldenstroem macroglobulinaemia, 11.8 percent in those with marginal zone lymphoma and 17.9 percent in the mantle cell lymphoma cohort.

The most common treatment-emergent side effects included fatigue (57 percent), nausea (48.2 percent) diarrhea (45.6 percent), vomiting (21.9 percent), headache (18.4 percent) and cough (23.7 percent); as well as laboratory abnormalities like anemia (36.8 percent), neutropenia (30.7 percent) and increased aspartate transaminase (36 percent), alanine transaminase (43.9 percent), total bilirubin (26.3 percent) and serum creatinine (57.9 percent)

The agent was dose reduced in 28 percent of patients and discontinued due to toxicity in 15 percent of patients.

“Entospletinib had limited single-agent activity with manageable toxicity in these patient populations,” the researchers wrote. “…The relatively low response rate as a single agent suggests that entospletinib should be investigated in combination with other agents."


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