Side by side

1. 1.Binds the chymotrypsin-like active site of the 26S proteasome.
2. 2.Blocks degradation of ubiquitin-tagged proteins, including I-kappa-B.
3. 3.Stabilised I-kappa-B keeps NF-kappa-B switched off, so survival signals fade.
4. 4.Cancer cells accumulate misfolded protein and die, while normal cells tolerate it better.
5. 5.Also affects the bone marrow microenvironment that supports myeloma cells.

• Multiple myeloma, first line and relapsed
• Mantle cell lymphoma
• AL amyloidosis
• Combination regimens with lenalidomide, dexamethasone or cyclophosphamide

• Substantially higher response and survival rates in myeloma than the older melphalan era
• Peripheral neuropathy in a third or more of patients, dose-limiting
• Thrombocytopenia that cycles with the dosing schedule
• Shingles reactivation without antiviral prophylaxis

• Peripheral sensory neuropathy, sometimes painful and persistent
• Thrombocytopenia and anaemia
• Herpes zoster reactivation
• Nausea, diarrhoea and constipation
• Fatigue
• Hypotension
• Rare pulmonary toxicity and heart failure

Research context only - a specialist cancer medicine. The standard schedule is 1.3 mg per square metre on days 1, 4, 8 and 11 of a 21-day cycle, given intravenously or subcutaneously, for up to eight cycles; trials used response rate, progression-free survival and overall survival as endpoints, with antiviral prophylaxis and platelet monitoring throughout.

Research context only