Thalidomide — Drug Monograph

Brand names: Thalomid

Drug class: Immunomodulatory Agent

Mechanism of Action

Thalidomide is an immunomodulatory agent with anti-angiogenic and antineoplastic activities. It inhibits the production of tumor necrosis factor-alpha (TNF-alpha), downregulates surface adhesion molecules involved in leukocyte migration, and inhibits angiogenesis by blocking VEGF and bFGF. It also induces oxidative stress-mediated DNA damage and apoptosis in myeloma cells. Additionally, it stimulates T-cell proliferation and increases IL-2 and IFN-gamma production.

FDA Indications

• In combination with dexamethasone for the treatment of patients with newly diagnosed multiple myeloma
• Acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL)
• Maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence

Common Side Effects

• Sedation
• Dizziness
• Constipation
• Peripheral neuropathy
• Fatigue
• Orthostatic hypotension
• Neutropenia
• Rash

Clinical Pearl

Thalidomide was the first "IMiD" but is now often bypassed for lenalidomide or pomalidomide due to its significant toxicity profile, particularly sedation and irreversible peripheral neuropathy. In the myeloma setting, aspirin or anticoagulation is mandatory to mitigate the high VTE risk. The sedative effect can be used to a clinical advantage by dosing at bedtime. Pharmacists must strictly enforce the REMS requirements, including ensuring male patients use condoms even if they have had a…

Related Therapies & Mechanisms

• Lenalidomide (Revlimid) — Immunomodulatory Agent · Myeloma
• Pomalidomide (Pomalyst) — Immunomodulatory Agent · Myeloma
• Interferon Alfa-2b (Intron A) — Immunomodulatory Agent
• Belantamab mafodotin (Blenrep) — Myeloma