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

• Published in: British journal of haematology 2019-01, Vol.184 (2), p.215-222
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Alanine; Alanine transaminase; Aspartate transaminase; Bilirubin; B‐cell receptor signalling inhibitors; Cough; Creatinine; Diarrhea; entospletinib; Fatigue; Female; Haematological Malignancy; Headache; Hematology; Humans; Indazoles - administration & dosage; Indazoles - adverse effects; indolent non‐Hodgkin lymphoma; Lymphocytes B; Lymphoma; Lymphoma, B-Cell, Marginal Zone - drug therapy; Lymphoma, B-Cell, Marginal Zone - enzymology; Lymphoma, B-Cell, Marginal Zone - pathology; Lymphoma, Follicular - drug therapy; Lymphoma, Follicular - enzymology; Lymphoma, Follicular - pathology; Lymphoma, Mantle-Cell - drug therapy; Lymphoma, Mantle-Cell - enzymology; Lymphoma, Mantle-Cell - pathology; Male; Mantle cell lymphoma; Middle Aged; Nausea; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - metabolism; Neutropenia; Patients; Protein-tyrosine kinase; Pyrazines - administration & dosage; Pyrazines - adverse effects; Research Paper; Spleen; spleen tyrosine kinase inhibitors; Syk Kinase - antagonists & inhibitors; Syk Kinase - metabolism; Syk protein; Thrombocytopenia; Toxicity; Transaminase; Vomiting; Waldenstrom Macroglobulinemia - drug therapy; Waldenstrom Macroglobulinemia - enzymology; Waldenstrom Macroglobulinemia - pathology
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.15552

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.