Bortezomib — Drug Monograph

Brand names: Velcade

Drug class: Proteasome Inhibitor

Mechanism of Action

First-in-class reversible inhibitor of the 26S proteasome chymotrypsin-like activity. The proteasome degrades ubiquitinated proteins including those controlling cell cycle (cyclin B, E), apoptosis (IκB), and transcription (NF-κB). Inhibition leads to accumulation of misfolded proteins (endoplasmic reticulum stress), activation of pro-apoptotic caspases, and inhibition of NF-κB-mediated survival signaling. Particularly active in myeloma cells with high immunoglobulin production.

FDA Indications

• Multiple myeloma — first-line (with melphalan and prednisone) and relapsed/refractory
• Mantle cell lymphoma — relapsed/refractory

Common Side Effects

• Peripheral neuropathy (dose-limiting; painful; predominantly sensory)
• Nausea, vomiting, diarrhea, constipation
• Fatigue
• Thrombocytopenia (nadirs on days 11–14; recovers by day 21)
• Neutropenia
• Herpes zoster reactivation (prophylaxis with acyclovir/valacyclovir required)

Clinical Pearl

The switch from IV to SC bortezomib is one of the most impactful quality-of-life improvements in myeloma treatment — the VISTA and other trials showed peripheral neuropathy rates of 38% (Grade ≥3: 17%) with IV vs. 24% (Grade ≥3: 6%) with SC, with equivalent efficacy. SC is now the standard route whenever possible.

Related Therapies & Mechanisms

• Carfilzomib (Kyprolis) — Proteasome Inhibitor · Myeloma
• Ixazomib (Ninlaro) — Proteasome Inhibitor · Myeloma
• Cyclophosphamide (Cytoxan) — Lymphoma
• Dexamethasone (Decadron) — Myeloma