Selinexor Being Developed for Treatment of Diffuse Large B-Cell Lymphoma
by Dr. C.H. Weaver M.D. 12/2018
Initial results on the activity of Selinexor were reported at the 2018 American Society of Hematology Annual Meeting from the Phase 2b SADAL (Selinexor Against Diffuse Aggressive Lymphoma) study which evaluated Selinexor in in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who had received a minimum of at least two prior multi-agent therapies and who are ineligible for transplantation.
Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. Selinexor recently received Fast Track designation from the FDA for development in patients with relapsed or refractory DLBCL.
In this group of advanced patients reported at ASH Selinexor was well tolerated and 30% of patients responded to treatment, 9.6% of patients attained a complete response to therapy that lasted a median of 23.0 months.
The results of single agent Selinexor in patients with heavily pretreated DLBCL are promising. Seliexor will represent another treatment option for b cell lymphomas and continued evaluation as a single agent and in combination with other anti-lymphoma therapies is ongoing. The manufacture plans to proceed to the FDA for approval in 2019.
Single Agent Oral Selinexor Demonstrates Deep and Durable Responses in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) in Both GCB and Non-GCB Subtypes: The Phase 2b SADAL Study Abstract Number/Publication ID: 1677