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 journalArticle

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)
JournalBritish Journal of Haematology
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Mantle-Cell Lymphoma
Waldenstrom Macroglobulinemia
Non-Hodgkin's Lymphoma
Follicular Lymphoma
Confidence Intervals
Disease-Free Survival
Lymphoma
B-Lymphocytes
Primary Headache Disorders
Aspartate Aminotransferases
Neutropenia
Alanine Transaminase
Bilirubin
Thrombocytopenia
Nausea
Vomiting
Fatigue
Anemia
Diarrhea
Creatinine

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

Andorsky, D. J., Kolibaba, K. S., Assouline, S., Forero-Torres, A., Jones, V., Klein, L. M., ... Sharman, J. P. (Accepted/In press). An open-label phase 2 trial of entospletinib in indolent non-Hodgkin lymphoma and mantle cell lymphoma. British Journal of Haematology. https://doi.org/10.1111/bjh.15552

An open-label phase 2 trial of entospletinib in indolent non-Hodgkin lymphoma and mantle cell lymphoma. / Andorsky, David J.; Kolibaba, Kathryn S.; Assouline, Sarit; Forero-Torres, Andres; Jones, Vicky; Klein, Leonard M.; Patel-Donnelly, Dipti; Smith, Mitchell; Ye, Wei; Shi, Wen; Yasenchak, Christopher A.; Sharman, Jeff P.

In: British Journal of Haematology, 01.01.2018.

Research output: Contribution to journalArticle

Andorsky, DJ, Kolibaba, KS, Assouline, S, Forero-Torres, A, Jones, V, Klein, LM, Patel-Donnelly, D, Smith, M, Ye, W, Shi, W, Yasenchak, CA & Sharman, JP 2018, 'An open-label phase 2 trial of entospletinib in indolent non-Hodgkin lymphoma and mantle cell lymphoma', British Journal of Haematology. https://doi.org/10.1111/bjh.15552
Andorsky, David J. ; Kolibaba, Kathryn S. ; Assouline, Sarit ; Forero-Torres, Andres ; Jones, Vicky ; Klein, Leonard M. ; Patel-Donnelly, Dipti ; Smith, Mitchell ; Ye, Wei ; Shi, Wen ; Yasenchak, Christopher A. ; Sharman, Jeff P. / An open-label phase 2 trial of entospletinib in indolent non-Hodgkin lymphoma and mantle cell lymphoma. In: British Journal of Haematology. 2018.
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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/Waldenstr{\"o}m 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.",
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