Velcade (Bortezomib) Dosing Regimens
The FDA-approved standard dose of bortezomib is 1.3 mg/m² administered as a 3-5 second intravenous bolus on days 1,4,8, and 11 of a 21-day cycle, with subcutaneous administration preferred to reduce peripheral neuropathy risk. 1
Multiple Myeloma Dosing
Newly Diagnosed Multiple Myeloma
For transplant-eligible patients, the VRD regimen (bortezomib, lenalidomide, dexamethasone) is the category 1 preferred induction therapy, consisting of bortezomib 1.3 mg/m² subcutaneously on days 1,8,15, lenalidomide 25 mg orally on days 1-14, and dexamethasone 20 mg on the day of and day after bortezomib, repeated every 3 weeks for four to six cycles before stem cell collection. 2
The SWOG S0777 trial demonstrated superior outcomes with VRD compared to lenalidomide-dexamethasone alone, achieving median progression-free survival of 43 months versus 30 months and median overall survival of 75 months versus 64 months 2
Subcutaneous administration is strongly preferred over intravenous to reduce peripheral neuropathy incidence 2, 1
For transplant-ineligible patients, VCD (bortezomib, cyclophosphamide, dexamethasone) is an alternative regimen with bortezomib 1.3 mg/m² on days 1,8,15, and 22 of a 28-day cycle, combined with dexamethasone 40 mg on days 1,8,15,22. 3
Relapsed/Refractory Multiple Myeloma
Bortezomib monotherapy at 1.3 mg/m² is given as an intravenous bolus on days 1,4,8, and 11 of a 21-day cycle, with a minimum 72-hour interval between doses to allow proteasome recovery. 1, 4
Responses typically appear by 6 weeks (2 cycles), and treatment should continue in responding patients until disease progression or unacceptable toxicity 4
For patients achieving complete remission, administer 2 additional cycles beyond confirmed complete response 4
If progressive disease occurs after 2 cycles or stable disease after 4 cycles, add dexamethasone 20 mg orally on the day of and day after each bortezomib dose 4
An alternative maintenance approach uses four standard cycles of bortezomib 1.3 mg/m² with dexamethasone, followed by weekly maintenance with bortezomib 1.6 mg/m² on days 1,8,15, and 22 every 36 days until progression. 5
- This short-course induction plus maintenance strategy achieved 58.3% partial response or better in relapsed/refractory patients 5
For combination therapy in relapsed disease, bortezomib 1.3 mg/m² on days 1,4,8,11 combined with dexamethasone 20 mg and continuous oral cyclophosphamide 50 mg daily achieved 90% overall response rate. 6
Mantle Cell Lymphoma Dosing
For previously untreated mantle cell lymphoma patients unsuitable for stem-cell transplantation, the VR-CAP regimen (bortezomib with rituximab, cyclophosphamide, doxorubicin, prednisone) uses bortezomib 1.3 mg/m² intravenously on days 1,4,8, and 11 of a 21-day cycle. 1, 7
The LYM-3002 trial demonstrated significantly improved progression-free survival with VR-CAP versus R-CHOP after 40 months median follow-up 7
Complete response rates were significantly higher with VR-CAP compared to standard R-CHOP therapy 7
Waldenström's Macroglobulinemia Dosing
Bortezomib-based therapy is recommended for patients with high IgM levels, symptomatic hyperviscosity, cryoglobulinemia, cold agglutinemia, amyloidosis, or renal impairment, ideally given once weekly subcutaneously. 8
- If urgent IgM reduction is needed, start with twice-weekly dosing for 1-2 cycles, then switch to once-weekly to reduce neurotoxicity risk 8
Dose Modifications
Hepatic Impairment
Use lower starting doses for patients with moderate or severe hepatic impairment, as specified in the FDA label. 1
- Monitor hepatic enzymes during treatment and interrupt therapy to assess reversibility if hepatotoxicity develops 1
Peripheral Neuropathy Management
Reduce dose or hold immediately upon development of painful neuropathy according to product monograph guidelines. 1, 4
Patients with pre-existing severe neuropathy should only receive bortezomib after careful risk-benefit assessment 1
Most toxicities are reversible if dose modification guidelines are followed promptly 4
Hematologic Toxicity
Monitor complete blood counts before each dose, with blood chemistries (electrolytes, creatinine) checked minimally on days 1 and 8 of each cycle. 4
- Thrombocytopenia and neutropenia are common; adjust dosing based on severity 1
Administration Guidelines
Check vital signs before and after each bortezomib dose. 4
Administer as a 3-5 second bolus intravenous injection or subcutaneous injection; never give intrathecally (contraindicated). 1
Ensure minimum 72-hour intervals between doses to allow normal proteasome function recovery. 1, 4
Critical Safety Monitoring
Mandatory antiviral prophylaxis is required due to high herpes zoster reactivation risk, particularly when combined with dexamethasone and cyclophosphamide. 6
Monitor for hypotension, especially in patients taking antihypertensives, with syncope history, or with dehydration. 1
Closely monitor patients with existing heart disease or cardiac risk factors, as worsening cardiac failure can occur. 1
Watch for acute respiratory syndromes and consider interrupting therapy for new or worsening pulmonary symptoms. 1
Monitor for posterior reversible encephalopathy syndrome; discontinue if visual or neurological symptoms develop and consider MRI imaging. 1
Assess for tumor lysis syndrome in patients with high tumor burden. 1