Thalidomide

Class: Immunomodulatory agent (IMiD) – first-generation.

• Mechanism of Action:
  • Anti-angiogenic: inhibits VEGF and FGF-mediated angiogenesis.
  • Immunomodulatory: enhances T-cell and NK-cell activity, inhibits TNF-α.
  • Direct anti-myeloma activity: induces apoptosis in plasma cells.

Clinical Uses

• Multiple myeloma: combination regimens (often with dexamethasone).
• Erythema nodosum leprosum (non-oncology indication).
• Investigational/rare: certain lymphomas or solid tumors.

Dosing

• Oral, typically 50–200 mg/day depending on regimen and patient tolerance.
• Dose adjustments for renal impairment may be required.

Toxicities

• Teratogenicity – extremely high risk; strict REMS program for pregnancy prevention.
• Peripheral neuropathy – dose- and duration-dependent; often irreversible.
• Sedation / fatigue – common early in therapy.
• Constipation – very common; prophylactic bowel regimen recommended.
• Thrombosis – increased risk of DVT/PE, especially when combined with steroids; consider anticoagulation prophylaxis.
• Other: rash, neutropenia, bradycardia, edema.

Monitoring

• CBC – for cytopenias.
• Neurologic assessment – baseline and periodic for neuropathy.
• VTE risk assessment – prophylaxis per guidelines.
• Pregnancy testing – mandatory for women of childbearing potential.
• Renal and hepatic function – periodically.

Summary

Thalidomide is an immunomodulatory and anti-angiogenic agent used mainly in multiple myeloma. It carries high teratogenicity, risk of peripheral neuropathy, sedation, constipation, and thrombosis, requiring strict monitoring and REMS compliance.