Selinexor—an anti-CD38 monoclonal antibody that reversibly inhibits nuclear export of tumor-suppressor proteins, growth regulators, and mRNAs of oncogenic proteins—is to be used in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies. The disease must be refractory to at least two proteasome inhibitors, an anti-CD38 monoclonal antibody, and at least two immunomodulating agents.

The clinical study of selinexor was based on part 2 of the STORM trial involving 122 patients—a multicenter, single-arm, open-label study of patients with relapsed or refractory multiple myeloma who had previously received three or more antimyeloma treatment regimens, including an alkylating agent, bortezomib, glucocorticoids, lenalidomide, pomalidomide, carfilzomib, and an anti-CD28 monoclonal antibody. In addition, the disease was also refractory to glucocorticoids, a proteasome inhibitor, an immunomodulating agent, an anti-CD38 monoclonal antibody, and any other last-line therapy. In this study, patients were treated with selinexor 80 mg in combination with dexamethasone on Days 1 and 3 of every week.

The approval of selinexor was based on safety and efficacy in a prespecified subgroup analysis of 83 patients with refractory disease. Study results showed the overall response rate was 25.3%, with one having complete response and no partial response. Four of those patients had very good partial responses, and 16 experienced partial responses; the median response duration was 3.8 months. The efficacy data are supported by additional information from another randomized, ongoing trial in patients with multiple myeloma.

The recommended starting dose of selinexor is 80 mg (four 20-mg tablets) taken by mouth on Days 1 and 3 of each week until disease progression or unacceptable toxicity. The recommended drug to take alongside is dexamethasone 20 mg by mouth with each dose of selinexor on Days 1 and 3 of each week. Pharmacists should advise patients to stay well hydrated during therapy and consider IV hydration for those who are at risk for dehydration during treatment. It is also recommended to provide prophylactic therapy with 5-HT3 antagonists and/or any other antinausea agents prior to and during treatment with selinexor. Additional monitoring recommendations include obtaining a CBC, standard blood chemistry, and body weight at baseline and during treatment.

The most common adverse reactions reported in at least 20% of patients included fatigue, nausea, decreased appetite, anemia, thrombocytopenia, decreased weight, hyponatremia, diarrhea, vomiting, neutropenia, leukopenia, constipation, upper respiratory tract infection, and dyspnea. Dosage reduction steps for adverse reactions are as follows: first reduction 100 mg once weekly, second reduction 80 mg once weekly, third reduction 60 mg once weekly, then discontinue.   

This study provides information on treatment options for those with relapsed or refractory multiple myeloma. The study presented an overall response rate of 25.3%, prompting the FDA to grant accelerated approval. Healthcare professionals should report all serious adverse events suspected to be associated with use to the FDA’s MedWatch Reporting System.

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