ASCO 2016: Selinexor Used in Combination Therapy May Benefit Multiple Myeloma Patients

Selinexor (KPT-330), which is the first drug in a new class of agents known as selective inhibitor of nuclear export compounds, may be helpful in treating patients with relapsed and refractory multiple myeloma, according to researchers at the Moffitt Cancer Center in Tampa.

They presented results from a phase 1 study of selinexor in combination with liposomal doxorubicin and dexamethasone in 13 patients with relapsed and refractory multiple myeloma at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, June 6, 2016, in Chicago (abstract 8013).

Selinexor is a first-in-class inhibitor of XPO1 and it has demonstrated activity in clinical trials for hematologic malignancies. Selinexor inhibits DNA damage repair. It works by trapping tumor suppressor proteins inside cancer cells, which causes them to die or stop growing. Preclinical studies have shown that selinexor is synergistic in combination with doxorubicin in mouse models of multiple myeloma.

The goals of the phase 1 trial were to determine the maximum tolerated dose and the recommended phase 2 dose for selinexor, liposomal doxorubicin and dexamethasone in patients with relapsed and refractory multiple myeloma who received two or more prior therapies including lenalidomide and a proteasome inhibitor. In addition to the induction phase, treatment includes a loading phase and a maintenance phase both consisting of selinexor and dexamethasone only.

Study investigator Rachid Baz, MD, who is an associate member of the Malignant Hematology Department at Moffitt, presented the results with 13 patients (median age of 59 years) who had a median of six prior lines (range: 2-9). The study showed no dose-limiting toxicities in dose level 1; however, two patients experienced dose-limiting toxicities on dose level 2. They suffered grade 4 thrombocytopenia and grade 3 nausea. In this study, the loading phase was shortened to 1 dose of selinexor (80mg) on day 7 and one out of the three patients experienced dose-limiting toxicities (grade 3 hyponatremia).

The study showed that the most common grade 3/4 toxicities were hyponatremia (54%), anemia (45%), thrombocytopenia (54%), and neutropenia (54%). In addition, other common grade 3/4 toxicities included diarrhea (18%), vomiting (27%), hyperglycemia (18%), and fatigue (18%). 

The researchers were able to evaluate 10 of the 13 patients for response. They found two patients achieved a very good partial response, two achieved a partial response, and two a minimal response. The remaining four had no response.

The investigators concluded that these preliminary responses in heavily pretreated patients support the continued investigation of this agent in patients with relapsed and refractory multiple myeloma.