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The results of an open-label, multicenter phase II trial on the use of entospletinib in indolent non-Hodgkin lymphoma (iNHL) and mantle cell lymphoma (MCL) were recently published in the British Journal of Haematology, by David Andorsky from the Rocky Mountain Cancer Centers, CO, USA, and colleagues.
Entospletinib (GS-9973) is a competitive inhibitor of the spleen tyrosine kinase (Syk). Syk is actively involved in the B-cell receptor (BCR) signalling pathway as it is believed to act upstream of both the Bruton’s tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K). Syk has been associated with lymphoma cell survival and proliferation in many B-cell malignancies and thus provides a great pharmacological target. The aim of this phase II trial (NCT01799889) was to assess the efficacy and tolerability of entospletinib in relapsed or refractory (R/R) iNHL or MCL patients. The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC). Key secondary endpoints included safety and overall response rate (ORR).
The results of this phase II trial indicate that entospletinib monotherapy leads to low response rates in R/R iNHL and MCL patients, despite its tolerable profile. The investigators proposed that entospletinib should be investigated in combination with other pharmacological agents in patients with hematological malignancies.
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Which of the following would most increase your confidence in referring patients with R/R large B-cell lymphoma for CAR T-cell therapy?