An open-label phase 2 trial of entospletinib in indolent non-Hodgkin lymphoma and mantle cell lymphoma

David J. Andorsky, Kathryn S. Kolibaba, Sarit Assouline, Andres Forero-Torres, Vicky Jones, Leonard M. Klein, Dipti Patel-Donnelly, Mitchell Smith, Wei Ye, Wen Shi, Christopher A. Yasenchak, Jeff P. Sharman

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)215-222
Number of pages8
JournalBritish journal of haematology
Volume184
Issue number2
DOIs
StatePublished - Jan 2019

Keywords

  • B-cell receptor signalling inhibitors
  • entospletinib
  • indolent non-Hodgkin lymphoma
  • mantle cell lymphoma
  • spleen tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Hematology

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