TY - JOUR
T1 - An Open-label, Phase II Trial of Entospletinib (GS-9973), a Selective Spleen Tyrosine Kinase Inhibitor, in Diffuse Large B-cell Lymphoma
AU - Burke, John M.
AU - Shustov, Andrei
AU - Essell, James
AU - Patel-Donnelly, Dipti
AU - Yang, Jay
AU - Chen, Robert
AU - Ye, Wei
AU - Shi, Wen
AU - Assouline, Sarit
AU - Sharman, Jeff
N1 - Funding Information:
The authors would like to thank Esteban Abella-Dominicis for his scientific contributions to the study during his tenure at Gilead Sciences, Inc. Editorial assistance was provided by Impact Communication Partners, Inc. This clinical study was supported by research funding from Gilead Sciences, Inc (Foster City, CA).
Publisher Copyright:
© 2018 The Authors
PY - 2018/8
Y1 - 2018/8
N2 - In an open-label, phase II study, we evaluated entospletinib monotherapy for patients with relapsed or refractory diffuse large B-cell lymphoma. Entospletinib had limited activity in these patients. Seventy-four percent of the patients experienced a grade ≥ 3 adverse event. Treatment was interrupted in 42% of the patients, and the drug was discontinued in 19% of the patients. Background: Entospletinib (GS-9973) is an oral, selective inhibitor of spleen tyrosine kinase. Entospletinib monotherapy was evaluated in a multicenter, phase II study of subjects with relapsed or refractory B-cell malignancy. Patients and Methods: The study included 43 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The participants received 800 mg of the original, monomesylate formulation of entospletinib twice daily as a starting dose; the doses could be reduced because of toxicity throughout the study. Results: No patient achieved a complete or partial response, 5 patients (12%) had stable disease, and 26 patients (60%) had progressive disease. Progression-free survival (PFS) at 16 weeks was 3.6% (95% confidence interval [CI], 0.3%-15.3%), and the median PFS was 1.5 months (95% CI, 1-1.7 months). The independent review committee–assessed nodal response for 27 evaluable patients showed a reduced tumor burden in 6 patients (22%). The median duration of entospletinib treatment for these 6 patients was 9 weeks (range, 3-24 weeks). One patient (4%) had a decrease of ≥ 50% in the sum of the product of the nodal diameters. The treatment-emergent adverse events occurring in ≥ 20% of the cohort were fatigue, nausea, decreased appetite, constipation, dyspnea, diarrhea, dehydration, cough, insomnia, and peripheral edema. The common laboratory abnormalities occurring in ≥ 20% of the subjects were lymphocytopenia, anemia, creatinine (chronic kidney disease), increased aspartate aminotransferase, hypoalbuminemia, total bilirubin, hyponatremia, leukopenia, increased alanine aminotransferase, increased alkaline phosphatase, and hyperglycemia. Conclusion: Entospletinib monotherapy at 800 mg twice daily demonstrated limited activity in patients with advanced, relapsed DLBCL.
AB - In an open-label, phase II study, we evaluated entospletinib monotherapy for patients with relapsed or refractory diffuse large B-cell lymphoma. Entospletinib had limited activity in these patients. Seventy-four percent of the patients experienced a grade ≥ 3 adverse event. Treatment was interrupted in 42% of the patients, and the drug was discontinued in 19% of the patients. Background: Entospletinib (GS-9973) is an oral, selective inhibitor of spleen tyrosine kinase. Entospletinib monotherapy was evaluated in a multicenter, phase II study of subjects with relapsed or refractory B-cell malignancy. Patients and Methods: The study included 43 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The participants received 800 mg of the original, monomesylate formulation of entospletinib twice daily as a starting dose; the doses could be reduced because of toxicity throughout the study. Results: No patient achieved a complete or partial response, 5 patients (12%) had stable disease, and 26 patients (60%) had progressive disease. Progression-free survival (PFS) at 16 weeks was 3.6% (95% confidence interval [CI], 0.3%-15.3%), and the median PFS was 1.5 months (95% CI, 1-1.7 months). The independent review committee–assessed nodal response for 27 evaluable patients showed a reduced tumor burden in 6 patients (22%). The median duration of entospletinib treatment for these 6 patients was 9 weeks (range, 3-24 weeks). One patient (4%) had a decrease of ≥ 50% in the sum of the product of the nodal diameters. The treatment-emergent adverse events occurring in ≥ 20% of the cohort were fatigue, nausea, decreased appetite, constipation, dyspnea, diarrhea, dehydration, cough, insomnia, and peripheral edema. The common laboratory abnormalities occurring in ≥ 20% of the subjects were lymphocytopenia, anemia, creatinine (chronic kidney disease), increased aspartate aminotransferase, hypoalbuminemia, total bilirubin, hyponatremia, leukopenia, increased alanine aminotransferase, increased alkaline phosphatase, and hyperglycemia. Conclusion: Entospletinib monotherapy at 800 mg twice daily demonstrated limited activity in patients with advanced, relapsed DLBCL.
KW - B-cell receptor signaling inhibitors
KW - DLBCL
KW - Hematologic malignancies
KW - Monotherapy
KW - Syk
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U2 - 10.1016/j.clml.2018.05.022
DO - 10.1016/j.clml.2018.05.022
M3 - Article
C2 - 29934062
AN - SCOPUS:85048855819
SN - 2152-2650
VL - 18
SP - e327-e331
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 8
ER -