Selinexor Triplet Under Study in Resistant Multiple Myeloma
Posted: Friday, February 5, 2021
The overall response rate in patients with heavily pretreated, relapsed, or refractory multiple myeloma was higher when they were treated with the novel agent selinexor plus pomalidomide and dexamethasone than those historically treated with pomalidomide and dexamethasone alone, according to the results of an open-label phase Ib/II trial presented during the virtual edition of the 2020 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 726). In addition, Christine I. Chen, MD, of Princess Margaret Cancer Centre, Toronto, and colleagues reported durable responses and improved progression-free survival with this all-oral combination.
Selinexor is a first-in-class oral selective inhibitor of nuclear export (SINE), which blocks XPO1, described the investigators. It forces the nuclear retention and activation of tumor suppressor proteins and ultimately causes cancer-cell apoptosis. This trial, STOMP, was a dose-escalation study with an expansion phase.
Of 52 enrolled patients (median age, 64 years), 47 were evaluable for response, and 44 had undergone autologous stem cell transplantation. Among the results, the team found the overall response rate was 58% in patients who were previously treated with lenalidomide and naive to pomalidomide; in comparison, the overall response rate was 31% in previously published data of a similar population treated with pomalidomide and dexamethasone alone. The median progression-free survival for the selinexor combination was 12.3 months in pomalidomide-naive patients compared with about 4 months, according to historical observation, for pomalidomide and dexamethasone alone in a similarly treated cohort.
The recommended phase II dose of selinexor was determined to be 60 mg once weekly, with dexamethasone at 40 mg once weekly and pomalidomide at 4 mg once daily, Dr. Chen and co-investigators stated. All treatment-related adverse effects were manageable with appropriate supportive care and/or dose modifications, they observed.
Disclosure: The authors’ disclosure information can be found at ash.confex.com.