Entospletinib monotherapy in patients with relapsed or refractory chronic lymphocytic leukemia previously treated with B-cell receptor inhibitors: results of a phase 2 study

Abstract

Entospletinib (GS-9973), an oral, selective inhibitor of spleen tyrosine kinase (SYK), was evaluated as monotherapy in this multicenter, phase 2 study (NCT01799889) of 49 patients with relapsed or refractory chronic lymphocytic leukemia (CLL), including those with Richter’s transformation (RT), who had received prior therapy with a B-cell receptor (BCR) inhibitor. Patients were treated with entospletinib 400 mg BID as the starting dose. Sixteen patients achieved partial response and 21 had stable disease. The overall response rate was 32.7% (95% confidence interval [CI]: 21.7–45.3%). The median progression-free survival (PFS) was 5.6 (95% CI: 3.7–8.3) months. Twenty-one (of 43) patients (48.8%) experienced nodal response. Adverse events (AEs) occurred in all patients; most commonly fatigue, diarrhea, and anemia. Entospletinib monotherapy has clinical activity for patients with CLL and RT who have relapsed following therapy with BCR inhibitors.

Keywords:

• SYK
• B-cell receptor inhibitors
• Richter’s transformation

Acknowledgments

We thank Beth Sesler, PhD, CMPP, for editorial assistance in preparing the manuscript and Steve Abella for his scientific contributions on the entospletinib development program.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2018.1562180.

Additional information

Funding

Financial support for this study was provided by Gilead Sciences, Inc.