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An open‐label phase 2 trial of entospletinib in indolent non‐Hodgkin lymphoma and mantle cell lymphoma
Author(s) -
Andorsky David J.,
Kolibaba Kathryn S.,
Assouline Sarit,
ForeroTorres Andres,
Jones Vicky,
Klein Leonard M.,
PatelDonnelly Dipti,
Smith Mitchell,
Ye Wei,
Shi Wen,
Yasenchak Christopher A.,
Sharman Jeff P.
Publication year - 2019
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15552
Subject(s) - medicine , mantle cell lymphoma , gastroenterology , neutropenia , follicular lymphoma , lymphoma , marginal zone b cell lymphoma , nausea , non hodgkin's lymphoma , adverse effect , chemotherapy , immunology , marginal zone , b cell , antibody
Summary Spleen tyrosine kinase (Syk) mediates B‐cell receptor signalling in normal and malignant B cells. Entospletinib is an oral, selective Syk inhibitor. Entospletinib monotherapy was evaluated in a multicentre, phase 2 study of patients with relapsed or refractory indolent non‐Hodgkin lymphoma or mantle cell lymphoma ( MCL ). Subjects received 800 mg entospletinib twice daily. Forty‐one follicular lymphoma ( FL ), 17 lymphoplasmacytoid lymphoma/Waldenström macroglobulinaemia ( LPL / WM ), 17 marginal zone lymphoma ( MZL ) and 39 MCL patients were evaluated. The primary endpoint was a progression‐free survival ( PFS ) rate (defined as not experiencing progression or death) at 16 weeks for patients with MCL and at 24 weeks for patients with FL , LPL / WM and MZL . The most common treatment‐emergent adverse events were fatigue, nausea, diarrhoea, vomiting, headache and cough. Common laboratory abnormalities were anaemia, neutropenia and thrombocytopenia; aspartate transaminase, alanine transaminase, total bilirubin and serum creatinine were all increased. PFS at 16 weeks in the MCL cohort was 63·9% [95% confidence interval ( CI ) 45–77·8%]; PFS at 24 weeks in the FL , LPL / WM , MCL and MZL cohorts was 51·5% (95% CI 32·8–67·4%), 69·8% (95% CI 31·8–89·4%), 56·6% (95% CI 37·5–71·8%) and 46·2% (95% CI 18·5–70·2%), respectively. Entospletinib had limited single‐agent activity with manageable toxicity in these patient populations.