Phase 1 study results of selinexor combination therapy; multiple myeloma

Selinexor is the first drug in a new class of agents known as Selective Inhibitor of Nuclear Export compounds. It works by inhibiting a protein found in the nucleus of cancer cells, activating tumor suppressors that kill the cancer cells. Normal cells are mostly spared. 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 are 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.

When the abstract was submitted, 11 patients with a median of five prior lines of therapy were enrolled in the study.

Dose limiting toxicities included low platelet counts, nausea, and low sodium levels. The most common adverse events possibly related to treatment were hyponatremia (54%), anemia (38%), thrombocytopenia (38%), neutropenia (38%), diarrhea (23%), vomiting (23%), hyperglycemia (15%) and fatigue (15%).

Preliminary results suggest that the selinexor combination regimen is active in relapsed and refractory multiple myeloma. Of 10 evaluable patients, two each achieved a very good partial response, a partial response, and a minimal response. The remaining four had no response.

Rachid Baz, M.D., associate member of the Malignant Hematology Department at Moffitt, will present the study results.