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.