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Clinical Trial
. 2019 Jan;184(2):215-222.
doi: 10.1111/bjh.15552. Epub 2018 Sep 5.

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

David J Andorsky  1 , Kathryn S Kolibaba  2 , Sarit Assouline  3 , Andres Forero-Torres  4 , Vicky Jones  5 , Leonard M Klein  6 , Dipti Patel-Donnelly  7 , Mitchell Smith  8 , Wei Ye  9 , Wen Shi  9 , Christopher A Yasenchak  10 , Jeff P Sharman  10
Affiliations
Clinical Trial

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

David J Andorsky et al. Br J Haematol. 2019 Jan.

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.

Keywords: B-cell receptor signalling inhibitors; entospletinib; indolent non-Hodgkin lymphoma; mantle cell lymphoma; spleen tyrosine kinase inhibitors.

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Figures

Figure 1
Figure 1
Independent review committee‐assessed progression‐free survival (PFS). (A) Follicular lymphoma (FL, n = 41). PFS rate at 24 weeks: 51·5% [95% confidence interval (CI) 32·8–67·4]; Median follow‐up: 3·6 months (1·6–5·6); Median PFS: 5·7 months (95% CI 3·6–11·2). (B) Lymphoplasmacytoid lymphoma/Waldenström macroglobulinaemia (LPL/WM; n = 17). PFS rate at 24 weeks: 69·8% (95% CI 31·8–89·4); Median follow‐up: 2·1 months (0–8·5); Median PFS: 10·9 months (95% CI 2·1–13·7). (C) Marginal zone lymphoma (MZL; n = 17). PFS rate at 24 weeks: 46·2% (95% CI 18·5–70·2); Median follow‐up: 3·6 months (1·9–6·9); Median PFS: 5·5 months (95% CI 3·5–22·1). (D) Mantle cell lymphoma (MCL; n = 39). Median PFS: 5·6 months (95% CI 3·6–8·9; Median follow‐up: 3·7 months (1·7–7·4).
Figure 2
Figure 2
Nodal responses (≥50% decrease from baseline in sum of product diameters) in the cohorts of patients with (A) indolent non‐Hodgkin lymphoma and (B) MCL. FL, follicular lymphoma; LPL, lymphoplasmacytoid lymphoma; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma; SPD, sum of product diameters.
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