What should a patient keep in mind while on bortezomib (Velcade) therapy?

Key Considerations for Patients on Bortezomib Therapy

Patients on bortezomib must take antiviral prophylaxis with acyclovir or valacyclovir to prevent herpes zoster reactivation, and should receive the medication subcutaneously on a weekly schedule to minimize peripheral neuropathy risk. 1

Critical Prophylactic Measures

Mandatory Antiviral Prophylaxis

• All patients treated with bortezomib or other proteasome inhibitors must take acyclovir or valacyclovir to suppress herpes virus reactivation 1, 2
• This prophylaxis should continue throughout the entire treatment course 1

Pneumocystis Prophylaxis

• Consider PJP prophylaxis when bortezomib is combined with rituximab-containing regimens 1

Administration Route and Schedule Optimization

Subcutaneous Administration is Strongly Preferred

• Subcutaneous administration significantly reduces peripheral neuropathy rates compared to intravenous delivery while maintaining equivalent efficacy 1, 2, 3
• The subcutaneous route reduces grade 3/4 peripheral neuropathy to 6-7% versus higher rates with IV administration 2
• Meta-analysis demonstrates 37% reduction in overall adverse events and 21% reduction in thrombocytopenia with subcutaneous versus IV administration 3

Weekly Dosing Reduces Toxicity

• Weekly dosing is preferred over twice-weekly schedules as it maintains efficacy while reducing grade 3/4 neuropathy to 6-7% 1, 2
• Twice-weekly dosing substantially increases neuropathy risk and often leads to treatment discontinuation 1
• In AL amyloidosis specifically, twice-weekly dosing is not recommended and likely results in therapy termination 1

Monitoring for Peripheral Neuropathy

Recognition and Risk Factors

• Peripheral neuropathy is the key dose-limiting toxicity, occurring in 35-47% of patients overall, with grade 3/4 severity in 8-13% 2
• The neuropathy is predominantly sensory (90%), though motor neuropathy occurs in 10% of cases 2, 4
• Major risk factors include cumulative dose, treatment schedule, older age, and pre-existing neuropathy 2, 4

Management Strategy

• Patients with pre-existing neuropathy should avoid bortezomib or receive attenuated dosing 1
• Approximately 70% of patients experience partial or complete reversibility with early recognition, dose reduction, or discontinuation 2
• For grade 2 neuropathy, reduce dose to 1.0 mg/m² 5
• Severe motor neuropathy may require steroids or intravenous immunoglobulin in addition to drug discontinuation 4

Cardiac Monitoring Considerations

Cardiotoxicity Risk

• Proteasome inhibitors carry an increased risk of cardiotoxicity and congestive heart failure 1
• Patients with cardiac involvement should initiate at lower doses (0.7-1.0 mg/m²) and uptitrate as tolerated 1
• Regular monitoring of cardiac biomarkers is essential, especially in high-risk disease 1
• Risk increases after cumulative doses exceeding 20 mg/m², requiring more intensive monitoring beyond this threshold 6

Hematologic Toxicity Management

Expected Cytopenias

• Neutropenia presents as grade 3/4 in up to 58% of patients in certain regimens 2
• Severe thrombocytopenia occurs in approximately 5% or less in frontline settings 2
• These effects are generally manageable and predictable with appropriate monitoring 2

Gastrointestinal Side Effects

• Diarrhea occurs in 52% of patients, with grade 3 severity in 26% in some combination regimens 2
• Nausea is common but typically manageable with antiemetics 1

Important Clinical Advantages

No Routine Anticoagulation Required

• Bortezomib has low risk of deep vein thrombosis compared to immunomodulatory agents, eliminating the need for routine anticoagulation prophylaxis 2
• This contrasts sharply with IMiDs (lenalidomide, pomalidomide, thalidomide), which require thromboprophylaxis 1

Specific Clinical Scenarios

• Bortezomib-based regimens are valuable in patients with renal failure, as proteasome inhibitors do not require dose adjustment for renal impairment 1, 2
• Effective in patients with adverse cytogenetic features and high-risk myeloma 1, 2

Drug Combination Considerations

Avoid Certain Combinations

• The risk of neuropathy increases substantially when bortezomib is combined with thalidomide 1
• Avoid bortezomib in patients with IgM-related peripheral neuropathy; consider alternatives like carfilzomib or bendamustine-rituximab 1

Stem Cell Preservation

• For transplant-eligible patients, bortezomib-based regimens do not compromise stem cell collection 1

Patient Education Points

• Adverse events are predictable and manageable with patient monitoring and appropriate supportive care 2
• Report any new numbness, tingling, or weakness in extremities immediately 2, 4
• Report any new shortness of breath, leg swelling, or chest discomfort promptly 1, 6
• Maintain compliance with antiviral prophylaxis throughout treatment 1