General Information

Xpovio (selinexor) is a nuclear export inhibitor.

Xpovio is specifically indicated for use in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.

Xpovio is specifically indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy.

Xpovio is supplied as a tablet or oral administration.

Multiple Myeloma: the recommended starting dosage of Xpovio is 80 mg (four 20 mg tablets) taken orally on Days 1 and 3 of each week until disease progression or unacceptable toxicity. The recommended starting dosage of dexamethasone is 20 mg taken orally with each dosage of Xpovio on Days 1 and 3 of each week. For additional information regarding the administration of dexamethasone, refer to its prescribing information. Each Xpovio dosage should be taken at approximately the same time of day, and each tablet should be swallowed whole with water. Do not break, chew, crush, or divide the tablets. If a dosage of Xpovio is missed or delayed, instruct patients to take their next dosage at the next regularly scheduled time. If a patient vomits a dosage of Xpovio, the patient should not repeat the dosage and the patient should take the next dosage on the next regularly scheduled day.

Diffuse Large B-Cell Lymphoma: the recommended dosage of Xpovio is 60 mg taken orally on Days 1 and 3 of each week until disease progression or unacceptable toxicity.

Clinical Results

The FDA approval of Xpovio for adults with relapsed or refractory multiple myeloma was given under accelerated approval status based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The accelerated approval was based on results from the Phase 2b STORM (Selinexor Treatment of Refractory Myeloma) trial, which was a multicenter, single-arm, open-label study of patients with RRMM. STORM Part 2 included 122 patients with RRMM. In STORM Part 2, a total of 122 patients were treated with Xpovio (80 mg) in combination with dexamethasone (20 mg) on Days 1 and 3 of every week. Treatment continued until disease progression, death, or unacceptable toxicity. The major efficacy outcome measure was overall response rate (ORR), as assessed by an Independent Review Committee based on the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma. The approval of Xpovio was based upon the efficacy and safety in a prespecified subgroup analysis of the 83 patients whose disease was refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab, as the benefit-risk ratio appeared to be greater in this more heavily pretreated population than in the overall trial population. For the STORM Part 2 study’s major efficacy outcome measure, the ORR was 25.3% in the subgroup of 83 patients, which included one stringent complete response, no complete responses, four very good partial responses and 16 partial responses. The median time to first response for these patients was 4 weeks and the median duration of response was 3.8 months.

The FDA approval of Xpovio for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) was given under accelerated approval status based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The accelerated approval was based on the Phase IIb SADAL (Selinexor Against Diffuse Aggressive Lymphoma) study. The multicenter, single-arm, open-label study enrolled 134 adults with relapsed or refractory DLBCL, not otherwise specified (NOS), after 2 to 5 systemic regimens. Data demonstrated a 29% overall response rate. Of those ORR successes, 13% had a complete response and 16% had partial responses. Key secondary endpoints included a median duration of response (DOR) in the responding patients. In the responding patients, 56% maintained a response at three months, 38% at six months, and 15% at 12 months.

Side Effects

Adverse effects associated with the use of Xpovio may include, but are not limited to, the following:

thrombocytopenia

fatigue

nausea

anemia

decreased appetite

decreased weight

diarrhea

vomiting

hyponatremia

neutropenia

leukopenia

constipation

dyspnea

upper respiratory tract infection

Mechanism of Action

Xpovio (selinexor) is a nuclear export inhibitor. In nonclinical studies, selinexor reversibly inhibits nuclear export of tumor suppressor proteins (TSPs), growth regulators, and mRNAs of oncogenic proteins by blocking exportin 1 (XPO1). XPO1 inhibition by selinexor leads to accumulation of TSPs in the nucleus, reductions in several oncoproteins, such as c-myc and cyclin D1, cell cycle arrest, and apoptosis of cancer cells. Selinexor demonstrated pro-apoptotic activity in vitro in multiple myeloma cell lines and patient tumor samples, and in murine xenograft models.