Bortezomib

Class: Proteasome inhibitor – reversible inhibitor of the 26S proteasome.

Mechanism of Action:

• • Inhibits ubiquitin-proteasome pathway, leading to accumulation of misfolded proteins → apoptosis, particularly in plasma cells.
  • Inhibits NF-κB activation, reducing tumor cell survival and angiogenesis.

Clinical Uses

• Multiple myeloma – newly diagnosed or relapsed/refractory.
• Mantle cell lymphoma (MCL) – relapsed/refractory.
• Occasionally used in other hematologic malignancies (investigational).

Dosing

• IV or subcutaneous: 1.3 mg/m² on days 1, 4, 8, and 11 of a 21-day cycle (twice-weekly schedule).
• Weekly or modified dosing possible for frail or elderly patients.
• Subcutaneous route preferred to reduce peripheral neuropathy.

Toxicities

• Peripheral neuropathy – cumulative, sensory > motor; dose-limiting.
• Myelosuppression – thrombocytopenia, neutropenia, anemia.
• Gastrointestinal – nausea, diarrhea, constipation.
• Fatigue, malaise – common.
• Herpes zoster reactivation – antiviral prophylaxis recommended.
• Rare: hypotension, pulmonary toxicity, liver enzyme elevations.

Monitoring

• CBC – for cytopenias.
• Neurologic assessment – baseline and periodic for neuropathy.
• Liver function tests – baseline and periodic.
• Infection prophylaxis – antiviral for VZV reactivation.
• Monitor for fluid retention and hypotension in high-risk patients.

Summary

Bortezomib is a first-in-class proteasome inhibitor used in multiple myeloma and mantle cell lymphoma. Key concerns are peripheral neuropathy, cytopenias, and herpes zoster reactivation, and subcutaneous administration plus prophylaxis can mitigate some risks.