Key points
- Bortezomib (Velcade) is an injectable drug that shuts down the protein clean-up system in cancer cells and kills them [1].
- It is used for multiple myeloma and a type of lymphoma (mantle cell lymphoma), and is part of common multi-drug myeloma combinations [1, 6].
- It is usually injected under the skin; this works just as well and causes less numbness of the hands and feet [1, 4].
- The main side effect is numbness, tingling or burning in the hands and feet; report it early so the dose can be adjusted, and it often gets better [1].
- It raises the risk of shingles; an antiviral tablet greatly lowers this risk [1].
What is this drug and how does it work?
For physicians
Bortezomib (brand name Velcade) is a reversible inhibitor of the 26S proteasome [1]. The proteasome is a large protein complex that degrades ubiquitinated proteins and so keeps the concentrations of many regulatory proteins in the cell in balance [1].
Proteasome inhibition stops this targeted degradation, disrupts several intracellular signalling pathways and can lead to cell death; bortezomib delayed tumour growth in laboratory models, including multiple myeloma [1].
In the APEX trial in relapsed myeloma, bortezomib gave higher response rates, longer time to progression and longer survival than high-dose dexamethasone [3], and in VISTA, adding it to melphalan and prednisone improved overall survival in newly diagnosed patients [2].
Which cancers is it used for?
Your doctor may prescribe this drug for:
- Newly diagnosed multiple myeloma (not suitable for high-dose treatment) [1]
- Newly diagnosed multiple myeloma in four-drug regimens [6, 7]
- Multiple myeloma that has come back [1]
- Newly diagnosed mantle cell lymphoma [1]
- Mantle cell lymphoma that has come back [1]
Whether it suits you depends on the type and stage of your cancer and your test results. Details of each use are in the section for doctors.
For physicians
| Cancer | Setting |
|---|---|
| Newly diagnosed multiple myeloma (not eligible for high-dose therapy) | With melphalan and prednisone, nine 6-week cycles [1] |
| Newly diagnosed multiple myeloma in four-drug regimens | Part of VRd with daratumumab (D-VRd) or isatuximab (Isa-VRd) [6, 7] |
| Relapsed multiple myeloma | Monotherapy or with dexamethasone; retreatment in patients who relapsed at least 6 months after prior bortezomib [1] |
| Newly diagnosed mantle cell lymphoma | With rituximab, cyclophosphamide, doxorubicin and prednisone (VR-CAP) [1] |
| Relapsed mantle cell lymphoma | Monotherapy [1] |
The D-VRd and Isa-VRd regimens appear in the labels of the anti-CD38 drugs (daratumumab and isatuximab); the bortezomib label only states “multiple myeloma in adults” in general [1].
| Cancer | Key evidence |
|---|---|
| Newly diagnosed multiple myeloma (not eligible for high-dose therapy) | VISTA: time to progression 24.0 vs 16.6 months (HR 0.48); HR for overall survival 0.61 [2] |
| Newly diagnosed multiple myeloma in four-drug regimens | PERSEUS: 48-month progression-free survival 84.3% with D-VRd vs 67.7% with VRd [6]; IMROZ: 60-month progression-free survival 63.2% with Isa-VRd vs 45.2% with VRd [7] |
| Relapsed multiple myeloma | APEX: time to progression 6.22 vs 3.49 months with dexamethasone (HR 0.55); 1-year survival 80% vs 66% [3] |
| Newly diagnosed mantle cell lymphoma | LYM-3002 (transplant-ineligible patients): median progression-free survival 24.7 vs 14.4 months with R-CHOP; HR 0.63 [5] |
| Relapsed mantle cell lymphoma | FDA label [1] |
How it is taken and dosing
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Treatment regimens and doses: index3 regimens
- Bortezomib is given only by healthcare staff, as an injection under the skin (in the thigh or abdomen) or a quick injection into a vein (3 to 5 seconds) [1].
- For injections under the skin, the site is changed each time; a new injection is given at least 2.5 cm (one inch) from the previous site and never into skin that is tender, bruised, red or hard [1]. A local reaction, mostly redness, may occur at the injection site [1].
- In many regimens the drug is given twice a week (for example on days 1, 4, 8 and 11) followed by a rest period; there must be at least 72 hours between two doses [1].
- The platelet count is checked before every dose [1].
- Ask your doctor about an antiviral medicine to prevent shingles [1].
- If you get tingling, burning or numbness in your hands or feet, be sure to tell your doctor before the next dose so the dose or schedule can be adjusted; do not stop treatment on your own [1].
- Administration: IV or subcutaneous only; intrathecal administration is contraindicated and has been fatal. Reconstitute the 3.5 mg vial with 3.5 mL (IV) or 1.4 mL (subcutaneous) of 0.9% sodium chloride; volume = dose (mg/m²) × BSA ÷ concentration. At least 72 hours between doses. Rotate subcutaneous sites (thigh or abdomen); for local reactions, use 1 mg/mL subcutaneously or the IV route [1].
- Contraindications: hypersensitivity to bortezomib, boron or mannitol [1].
- Herpes zoster prophylaxis: consider antiviral prophylaxis; in randomised myeloma trials, zoster occurred in 6 to 11% with bortezomib vs 3 to 4% in controls [1].
- Monitoring: frequent CBC and platelets before each dose; liver enzymes; blood pressure (hypotension, especially with antihypertensives, a history of syncope or dehydration); symptoms of neuropathy, heart failure, pulmonary symptoms, tumour lysis syndrome with high tumour burden, and TTP/HUS (stop if suspected) [1].
- Dose levels: 1.3 → 1 → 0.7 mg/m² [1].
- Relapsed disease: grade 3 non-haematological or grade 4 haematological toxicity (other than neuropathy): hold and, once resolved, resume with a 25% reduction [1].
- Peripheral neuropathy: grade 1 without pain: no change; grade 1 with pain or grade 2: reduce to 1 mg/m²; grade 2 with pain or grade 3: hold until improved and resume at 0.7 mg/m² once weekly; grade 4: discontinue permanently. With pre-existing neuropathy or high risk, consider starting subcutaneously [1].
- Hepatic impairment: mild (bilirubin ≤1.5 times the upper limit): no change; moderate (above 1.5 to 3 times) or severe (above 3 times): 0.7 mg/m² in the first cycle, then increase to 1 or decrease to 0.5 mg/m² according to tolerance [1].
- Renal impairment: no clinically meaningful pharmacokinetic difference (including administration after dialysis) [1].
- Interactions: avoid strong CYP3A4 inducers (rifampicin lowered exposure by about 45%); with strong CYP3A4 inhibitors, monitor for toxicity and consider a dose reduction [1].
For physicians
Standard dosing and combination regimens (FDA label)
Bortezomib in relapsed myeloma or mantle cell lymphoma
Monotherapy; for myeloma retreatment, alone or with dexamethasoneCycle length: Every 21 days
Monotherapy; for myeloma retreatment, alone or with dexamethasone
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Bortezomib | 1.3 mg/m² | Subcutaneous (2.5 mg/mL) or IV bolus over 3 to 5 seconds (1 mg/mL) | Days 1, 4, 8 and 11 |
Retreatment: in myeloma that previously responded to bortezomib and relapsed at least 6 months after it ended, at the last tolerated dose, days 1, 4, 8 and 11 every 3 weeks for up to 8 cycles [1].
VMP: bortezomib + melphalan + prednisone
Newly diagnosed multiple myeloma
Newly diagnosed multiple myeloma
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cycles 1 to 4 | |||
| Bortezomib | 1.3 mg/m² | Subcutaneous (2.5 mg/mL) or IV bolus over 3 to 5 seconds (1 mg/mL) | Days 1, 4, 8, 11, 22, 25, 29 and 32 |
| Cycles 5 to 9 | |||
| Bortezomib | 1.3 mg/m² | Subcutaneous (2.5 mg/mL) or IV bolus over 3 to 5 seconds (1 mg/mL) | Days 1, 8, 22 and 29 |
| All cycles | |||
| Melphalan | 9 mg/m² | Oral | Days 1 to 4 |
| Prednisone | 60 mg/m² | Oral | Days 1 to 4 |
Before each cycle: platelets ≥70,000 and ANC ≥1000 per µL and non-haematological toxicity grade ≤1 or baseline. On days other than day 1, if platelets are ≤30,000 or ANC ≤750, withhold the bortezomib dose; if several doses are withheld in consecutive cycles, reduce by one level. Prolonged grade 4 neutropenia or thrombocytopenia, or thrombocytopenia with bleeding: reduce melphalan by 25% in the next cycle [1].
VcR-CAP: bortezomib + rituximab + cyclophosphamide + doxorubicin + prednisone
Newly diagnosed mantle cell lymphomaCycle length: Every 21 days
Newly diagnosed mantle cell lymphoma
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Bortezomib | 1.3 mg/m² | IV, before rituximab | Days 1, 4, 8 and 11 |
| Rituximab | 375 mg/m² | IV | Day 1 |
| Cyclophosphamide | 750 mg/m² | IV | Day 1 |
| Doxorubicin | 50 mg/m² | IV | Day 1 |
| Prednisone | 100 mg/m² | Oral | Days 1 to 5 |
Before day 1 of each cycle (except cycle 1): platelets ≥100,000, ANC ≥1500 per µL, haemoglobin ≥8 g/dL and non-haematological toxicity grade ≤1. On days 4, 8 and 11: grade ≥3 neutropenia or platelets below 25,000: hold for up to 2 weeks until ANC ≥750 and platelets ≥25,000, then reduce by one level (discontinue if not recovered); grade ≥3 non-haematological toxicity: hold until grade ≤2 and reduce by one level [1].
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Side effects
The most common side effects:
- Nausea, diarrhoea, constipation, vomiting and poor appetite [1].
- Tiredness and fever [1].
- Numbness, tingling or burning in the hands and feet (neuropathy) in about a third to a half of patients; tell your doctor early so the dose can be adjusted [1].
- Low platelets and white blood cells, which show up in blood tests [1].
- Shingles: this is why an antiviral medicine is usually given to prevent it [1].
For physicians
| Adverse reaction | Relapsed myeloma: IV bortezomib monotherapy (331 patients) | Newly diagnosed myeloma: bortezomib + melphalan and prednisone (340 patients) |
|---|---|---|
| Nausea | 52% [1] | 39% [1] |
| Diarrhoea | 52% [1] | 35% [1] |
| Fatigue | 39% [1] | 25% [1] |
| Peripheral neuropathy | 35% [1] | 46% [1] |
| Thrombocytopenia | 33% [1] | 48% [1] |
| Constipation | 30% [1] | 23% [1] |
| Vomiting | 29% [1] | 26% [1] |
| Anorexia | 21% [1] | 19% [1] |
| Neutropenia | 18% [1] | 47% [1] |
| Pyrexia | 20% [1] | 16% [1] |
| Herpes zoster | Not in this list | 11% [1] |
These figures are for intravenous injection. In the trial comparing subcutaneous with intravenous use, grade 2 or higher peripheral neuropathy occurred in 24% vs 39% and grade 3 or higher in 6% vs 15%, and a local reaction (mostly redness) was seen in 6% of patients in the subcutaneous arm [1].
Serious side effects
These are less common but serious; tell your team early if you notice any sign of them:
- Severe neuropathy: nerve pain, weakness or trouble walking; it gets better in about half of patients when the dose is lowered or stopped [1].
- Low blood pressure: dizziness or fainting when standing up, especially if you are dehydrated or take blood pressure medicines [1].
- Heart or lung problems: shortness of breath, swollen legs or a new cough [1].
- Bleeding when platelets are low: bruising, black stools or a severe headache [1].
- A severe headache with seizures or blurred vision, liver damage and harm to an unborn baby [1].
For physicians
Bortezomib has no boxed warning, but the FDA label lists these warnings [1]:
- Peripheral neuropathy: mainly sensory (burning, hypo- or hyperaesthesia, paraesthesia, neuropathic pain or weakness), but severe sensory and motor cases have been reported. With dose adjustment or discontinuation, improvement or resolution was reported in 48% of patients with grade 2 or higher neuropathy in the phase 3 trial of bortezomib vs dexamethasone [1].
- Hypotension: hypotension (including orthostatic hypotension) occurred in 8% of patients, throughout treatment; a history of syncope, antihypertensive drugs and dehydration increase the risk [1].
- Cardiac toxicity: new or worsening heart failure and reduced left ventricular ejection fraction [1].
- Pulmonary toxicity: acute respiratory distress syndrome, pneumonitis and pulmonary hypertension; some cases have been fatal [1].
- Posterior reversible encephalopathy syndrome (PRES) with seizures, hypertension, headache, confusion or visual disturbance [1].
- Gastrointestinal toxicity including nausea, diarrhoea, constipation, vomiting and ileus [1].
- Thrombocytopenia and neutropenia in a cyclical pattern, with the nadir after the last dose of each cycle; gastrointestinal and intracerebral haemorrhage have been reported during thrombocytopenia [1].
- Tumour lysis syndrome, hepatotoxicity and thrombotic microangiopathy (TTP/HUS), sometimes fatal [1].
- Embryo-fetal toxicity based on mechanism of action and animal studies [1].
When should I call my doctor?
- New or worsening tingling, burning, numbness, pain or weakness in the hands or feet [1].
- Dizziness, light-headedness or fainting, especially when standing up; do not drive if this happens [1].
- Shortness of breath, cough or swollen legs (a possible lung or heart problem) [1].
- Seizures, a severe headache, confusion or a sudden change in vision [1].
- Fever, unusual bleeding or bruising, severe constipation or loss of appetite, or a rise in blood pressure [1].
- A rash, a severe injection-site reaction or skin pain [1].
- Pregnancy, yours or your partner's, during treatment or for up to 7 months afterwards [1].
Interactions, pregnancy and precautions
- Other medicines: the tuberculosis drug rifampicin reduces the effect of bortezomib and should not be taken with it; antifungal drugs such as ketoconazole raise its level and may increase side effects [1]. Give your doctor a list of all your medicines [1].
- Diabetes: people taking diabetes tablets may have low or high blood sugar; check your blood sugar regularly [1].
- Blood pressure: if you take blood pressure medicines, they may need adjusting; drink enough fluids [1].
- Pregnancy: a pregnancy test is done before starting. Women who could become pregnant should use effective contraception for 7 months after the last dose, and men with a partner who could become pregnant for 4 months [1].
- Breastfeeding: do not breastfeed during treatment and for 2 months after the last dose [1].
- Driving: do not drive or operate machinery if you feel tired, dizzy or faint, or have low blood pressure on standing [1].
Frequently asked questions
Is an injection under the skin or into a vein better?
Will the tingling and numbness in my hands and feet go away?
Why do I need to take an antiviral medicine?
Bortezomib raises the risk of the shingles virus becoming active again. In a large study, a preventive antiviral medicine made shingles much less common [1].
Why do I feel dizzy when I stand up?
Can I have bortezomib again?
Yes; in myeloma patients who previously responded to bortezomib and relapsed at least 6 months after it ended, retreatment at the last tolerated dose can be considered [1].
Scientific evidence
Show detailsHide
Key studies
3 itemsInternational Myeloma Working Group updated criteria for the diagnosis of multiple myeloma
Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma
Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma
Related cancer types
Treatment regimens (physicians)
References
7 referencesShow all references, 6 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1VELCADE (bortezomib) for injection, for subcutaneous or intravenous use — Prescribing InformationSource Back to text: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101
- 2Bortezomib plus Melphalan and Prednisone for Initial Treatment of Multiple Myeloma
- 3Bortezomib or High-Dose Dexamethasone for Relapsed Multiple Myeloma
- 4Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study
- 5Bortezomib-Based Therapy for Newly Diagnosed Mantle-Cell Lymphoma
- 6
- 7
This page is based on reputable scientific sources and was last updated on 27 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.
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