Pomalidomide — Drug Monograph

Brand names: Pomalyst

Drug class: Immunomodulatory Agent

Mechanism of Action

Third-generation immunomodulatory imide drug (IMiD). Like thalidomide and lenalidomide, pomalidomide binds cereblon (CRBN) — the substrate receptor of the CRL4-CRBN E3 ubiquitin ligase complex. This redirects the E3 ligase to ubiquitinate and proteasomally degrade two lymphoid transcription factors: IKZF1 (Ikaros) and IKZF3 (Aiolos). Ikaros/Aiolos are essential for myeloma cell survival; their depletion causes myeloma cell apoptosis. Pomalidomide is more potent than lenalidomide at CRBN binding and more effective in lenalidomide-refractory myeloma. Additional activities include…

FDA Indications

• Multiple myeloma — relapsed/refractory after ≥2 prior therapies including lenalidomide and a proteasome inhibitor (± dexamethasone)
• Multiple myeloma — in combination with daratumumab and dexamethasone (DPd — APOLLO trial)
• Kaposi sarcoma — AIDS-related or non-AIDS-related, after failure of ≥1 prior systemic therapy

Common Side Effects

• Neutropenia (dose-limiting; ~50%)
• Anemia
• Thrombocytopenia
• Fatigue
• Constipation
• Peripheral neuropathy (less common than thalidomide)
• Muscle weakness
• Upper respiratory tract infections

Clinical Pearl

Pomalidomide is the preferred IMiD for lenalidomide-refractory myeloma. Thromboprophylaxis is mandatory — the choice of agent depends on patient risk: aspirin 81 mg/day for standard-risk patients (no prior VTE, ambulatory, low-risk VTE profile); LMWH or anticoagulation for high-risk patients (prior DVT/PE, immobility, multiple myeloma-related risk factors). Unlike thalidomide, pomalidomide rarely causes significant peripheral neuropathy at standard doses.

Related Therapies & Mechanisms

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