selinexor — Drug Monograph
Brand names: Xpovio
Drug class: Other
Mechanism of Action
Selinexor is a first-in-class selective inhibitor of nuclear export (SINE) that covalently binds to XPO1 (exportin-1, CRM1), the primary nuclear export receptor responsible for shuttling tumor suppressor proteins out of the nucleus. Inhibition of XPO1 causes nuclear accumulation and functional reactivation of key tumor suppressors including p53, FOXO1/3, IκB, RB1, and CDKN1A (p21), as well as reduction of nuclear export of oncogenic mRNAs (including MYC, MDM2, BCL-2 mRNAs). This results in cell cycle arrest and apoptosis selectively in cancer cells with aberrant XPO1-dependent export activity.
FDA Indications
- Relapsed or refractory multiple myeloma (RRMM) in adults who have received ≥4 prior therapies including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 antibody, in combination with low-dose dexamethasone — approved Jul 2019 (STORM trial)
- Relapsed or refractory multiple myeloma in combination with bortezomib and dexamethasone (SVd regimen) after ≥1 prior therapy — approved Dec 2020 (BOSTON trial)
- Relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, in adults who have received ≥2 prior therapies — approved Jun 2020 (SADAL trial)
Common Side Effects
- Nausea (~72%)
- Fatigue (~68%)
- Thrombocytopenia (~74%)
- Anorexia (~60%)
- Weight loss
- Vomiting (~49%)
- Diarrhea
- Hyponatremia (~39%)
- Neutropenia
- Anemia
- Constipation
- Dyspnea
Clinical Pearl
GI toxicity with selinexor is predictable and largely manageable with aggressive prophylaxis — the standard of care includes a 5-HT3 antagonist (ondansetron 8 mg) plus dexamethasone 8 mg taken 30–60 minutes before every selinexor dose, with an NK1 antagonist added for higher-dose regimens. Hyponatremia occurs in ~30–40% of patients and is thought to be a CNS-mediated syndrome of inappropriate antidiuretic hormone (SIADH) effect; sodium supplementation or fluid restriction may be required. The…
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