Selinexor

Drug class: Selective Inhibitor of Nuclear Export (SINE).

  • Mechanism of action:
    • Inhibits exportin 1 (XPO1/CRM1), a nuclear export protein.
    • Prevents transport of tumor suppressor proteins (e.g., p53, RB, FOXO, IκB) out of the nucleus.
    • Leads to accumulation of tumor suppressors in the nucleus, triggering cell-cycle arrest and apoptosis of malignant cells.

Indications (FDA/EMA approved):

  • Multiple Myeloma:
    • In combination with dexamethasone for relapsed/refractory MM after ≥4 prior therapies (including PI, IMiD, and CD38 antibody).
    • In combination with bortezomib + dexamethasone (SVd) for relapsed/refractory MM after ≥1 prior therapy.
  • Diffuse Large B-Cell Lymphoma (DLBCL):
    • Relapsed/refractory, not eligible for transplant.

Dosing:

  • Multiple myeloma (SVd regimen): 100 mg orally once weekly (Day 1 & 3 in some regimens).
  • With dexamethasone (doublet): 80 mg orally once weekly (with dex).
  • Take with food; swallow whole (no crushing).
  • Dose modifications for toxicity (especially cytopenias, GI effects).

Key adverse effects:

  • GI: Nausea, vomiting, anorexia, diarrhea (very common, requires prophylaxis/supportive care).
  • Hematologic: Thrombocytopenia, neutropenia, anemia.
  • Fatigue, hyponatremia, weight loss.
  • Serious: CNS toxicity (confusion, dizziness), infections.

Pharmacist notes:

  • Supportive care is critical:
    • Antiemetics (5-HT3 antagonist + olanzapine/other agents) recommended prophylactically.
    • Monitor hydration, nutrition, electrolytes (especially sodium).
  • Oral administration makes it convenient, but adherence and GI tolerance can be challenging.
  • Monitor: CBC, electrolytes (Na), weight, performance status.

High-yield points for exam/clinical practice:

  • Target: Exportin 1 (XPO1).
  • Use: Heavily pretreated MM ± DLBCL.
  • Toxicities: GI (nausea/vomiting), cytopenias, hyponatremia.
  • Pharmacist role: Aggressive supportive care and close monitoring.
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