Selinexor
Indications
Selinexor is used for:
Multiple Myeloma
Adult Dose
Multiple Myeloma
Indicated in combination with dexamethasone for adults with relapsed or refractory multiple myeloma (RRMM) who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody
80 mg PO plus dexamethasone 20 mg PO on Days 1 and 3 of each week
Continue until disease progression or unacceptable toxicity
Concomitant treatment
Maintain adequate fluid and caloric intake throughout treatment
Consider IV hydration for patients at risk of dehydration
Provide prophylactic concomitant treatment with a 5–HT3 antagonist and/or other antinausea agents before and during treatment
Hepatic impairment
Mild: No significant differences in pharmacokinetics observed
Moderate-to-severe: Effect on pharmacokinetics unknown
Child Dose
Renal Dose
Renal impairment
Mild-to-severe (CrCl 15-89 mL/min): No significant differences in pharmacokinetics observed
ESRD (CrCl <15 mL/min) or hemodialysis: Effect on pharmacokinetics unknown
Administration
May take with or without food
Contra Indications
Precautions
High incidence of thrombocytopenia reported; median time to onset of first event was 22 days; some patients experienced bleeding; rare reports of death resulting from fatal hemorrhage
Neutropenia commonly reported, potentially increasing infection risk
Nausea and/or vomiting commonly occurs; follow recommendations for adequate hydration and prophylactic antiemetics
Diarrhea commonly reported; monitor for dehydration and provide supportive care as required
Anorexia and weight loss reported
Hyponatremia may rapidly occur (median onset 8 days) and may be severe
Infections reported; most infections were not associated with neutropenia and were caused by nonopportunistic organisms
Neurological toxicity may occur, including dizziness, syncope, depressed level of consciousness, and mental status changes (including delirium and confused state)
Embryofetal toxicity can occur
Pregnancy-Lactation
Pregnancy
Based on animal studies and its mechanism of action, selinexor can cause fetal harm if administered to pregnant women
Verify pregnancy status of females of reproductive potential before initiating selinexor
Animal studies
Administration to pregnant rats during organogenesis resulted in structural abnormalities and alterations to growth at exposures below those clinically recommended for humans
Contraception
Females of reproductive potential: Use effective contraception during treatment and for 1 week after the last dose
Males with female partner of reproductive potential: Use effective contraception during treatment and for 1 week after the last dose
Infertility
Based on animal studies, selinexor may impair fertility in females and males
Lactation
No data are available regarding the presence of selinexor or its metabolites in human milk, or their effects on the breastfed child or milk production
Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 1 week after the last dose
Interactions
Adverse Effects
Side effects of Selinexor :
>10% (All Grades)
Thrombocytopenia (74%)
Fatigue (73%)
Nausea (72%)
Anemia (59%)
Decreased appetite (53%)
Weight decreased (47%)
Diarrhea (44%)
Vomiting (41%)
Hyponatremia (39%)
Neutropenia (34%)
Leukopenia (28%)
Constipation (25%)
Dyspnea (24%)
Upper respiratory tract infection (21%)
Cough (16%)
Mental status changes (16%)
Pyrexia (16%)
Hyperglycemia (15%)
Dizziness (15%)
Insomnia (15%)
Lymphopenia (15%)
Dehydration (14%)
Hypercreatinemia (14%)
Pneumonia (13%)
Epistaxis (12%)
Hypokalemia (12%) Dysgeusia (11%)
>10% (Grades ≥3)
Thrombocytopenia (61%)
Anemia (40%)
Fatigue (22%)
Hyponatremia (22%)
Neutropenia (21%)
Leukopenia (11%)
1-10% (All Grades)
Blurred vision (10%)
Headache (10%)
Mechanism of Action
Selective inhibitor of nuclear export (SINE) of tumor suppressor proteins (TSPs), growth regulators, and mRNAs of oncogenic proteins by blocking exportin 1 (XPO1)
XPO1 inhibition leads to accumulation of TSPs in the nucleus, reductions in several oncoproteins (eg, c–myc, cyclin D1), cell cycle arrest, and apoptosis of cancer cells
Selinexor demonstrated proapoptotic activity in vitro in multiple myeloma cell lines, patient tumor samples, and murine xenograft model