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