VELCADE® became the first in a class of drugs called proteasome inhibitors to be approved by the FDA for use in myeloma. 

Who Is a Candidate for Velcade?

Velcade is used throughout the myeloma disease course, in both newly diagnosed myeloma as well as relapsed/refractory disease.

Velcade can be used alone, in combination with dexamethasone, or as part of a more complex multi-drug regimen. Numerous clinical trials conducted over the years have shown that administration of Velcade on a once-weekly schedule in combination with other anti-myeloma agents is associated with reduction in side effects, without reduction in efficacy, when compared to twice-weekly Velcade.

How Does Velcade Work?

Velcade works by inhibiting enzyme complexes called proteasomes. Both normal cells and cancer cells contain proteasomes, which break down damaged and unwanted proteins into smaller components. Proteasomes also carry out the regulated breakdown of undamaged proteins in the cell, a process that is necessary for the control of many critical cellular functions. These smaller protein components are then used to create new proteins required by the cell. Proteasomes can be thought of as crucial to the cell’s “recycling” of proteins.

When Velcade inhibits proteasome function, the normal balance within a cell is disrupted. This disruption results in a number of effects on the cell, some of which are still being studied. When proteasomes are inhibited, myeloma cells stop dividing. Proteasome inhibition also causes myeloma cells to stop producing chemicals that stimulate other myeloma cells. Myeloma cells are more sensitive to these effects than normal cells, so myeloma cells die while normal cells can recover.

How Is Velcade Given?

Velcade is given at the doctor’s office or a clinic. Numerous clinical trials conducted in the course of the past decade have shown that administration of Velcade on a weekly schedule in combination with other anti-myeloma agents is associated with reduction in side effects,  without reduction in efficacy.
Velcade can be given as an intravenous (IV - into the vein) infusion injected through either a peripheral IV line (usually in the arm) or a central IV line (usually in the chest, also known as a central venous catheter). Velcade is also approved to be given as a subcutaneous (SQ, sometimes written SC – under the skin) injection, commonly known as a “shot.”

What Is the Dose and Schedule for Velcade?

When taking Velcade, our doctor may choose to lower your dose of the drug and/or to change your treatment schedule if you experience side effects, have pre-existing medical problems, or are elderly or frail. Your doctor may also choose to skip a scheduled dose to reduce the severity of a side effect before continuing treatment.

The following two tables show how Velcade may be dosed:

Table 1 Velcade Treatment for Frail Patients* 

Go-Go Moderate-Go Slow-Go
Dose level 0 Dose level 1  Dose level 2
No risk factors At least 1-2 risk factors At least one risk factor + any Grade 3–4 non-hematologic adverse event

*Note: Frail patients here are defined as having the following risk factors:
•    Age: over 75 years.
•    Mild, moderate, or severe frailty: help needed for household and personal care.
•    Comorbidities and organ dysfunction: cardiac, pulmonary, hepatic, and/or renal

Table 2 Velcade Treatment for All Other Patients*

Dose level 0

Age < 65 years

Dose level 1

Age 65-75 years

Dose level 2

Age > 75 years

1.3 mg/m²; days 1, 4, 8, 11 3 weeks 1.3 mg/m²; days 1, 4, 8, 11 3 weeks
1.3 mg/m²; days 1, 8, 15, 22 5 weeks
1.0–1.3 mg/m²; days 1, 8, 15, 22 5 weeks

*Note: Your doctor will monitor your side effects. If you have what is determined to be Grade 3 or 4 adverse events (or, side effects), your doctor may discontinue use of Velcade. Your doctor will then wait for a Grade 1 adverse event and then opt to restart treatment.

Possible Side Effects

The most common side effects of Velcade (reported at an incidence ≥20% in clinical studies) include nausea, diarrhea, thrombocytopenia, neutropenia, peripheral neuropathy, fatigue, neuralgia, anemia, leukopenia, constipation, vomiting, lymphopenia, rash, pyrexia, and anorexia.

Serious side effects can include:

Nerve problems (peripheral neuropathy). Velcade can cause damage to the nerves, a condition called peripheral neuropathy. You may feel muscle weakness, tingling, burning, pain, and loss of feeling in your hands and feet, any of which can be severe. Tell your doctor if you notice any of these symptoms. Your doctor may change the dose and/or schedule of Velcade or stop it altogether. If you have peripheral neuropathy before starting Velcade, your doctor could consider giving you Velcade subcutaneously.

Low blood pressure (hypotension). Velcade can cause a drop in blood pressure. Tell your doctor if you have low blood pressure, feel dizzy, or feel as though you might faint. If you are taking drugs that lower blood pressure, your medications might need to be adjusted. If you are not drinking enough liquids, your doctor may need to administer IV fluids.

Heart problems (cardiac toxicity). Treatment with Velcade can cause or worsen heart rhythm problems and heart failure. Your doctor may closely monitor you if you have, or are at risk for, heart disease. Tell your doctor if you experience chest pressure or pain, palpitations, swelling of your ankles or feet, or shortness of breath

Lung problems (pulmonary toxicity). There have been reports of lung disorders in people receiving Velcade. Some of these events have been fatal. Tell your doctor if you experience any cough, shortness of breath, wheezing, or difficulty breathing.

Brain swelling (Posterior Reversible Encephalopathy Syndrome— PRES). There have been reports of a rare, reversible condition involving the brain, called PRES, in people treated with Velcade. People with PRES can have seizures, high blood pressure, headaches, tiredness, confusion, blindness, or other vision problems. Treatment with Velcade should be stopped in cases of PRES. It is not known whether restarting Veclade therapy in patients previously experiencing this complication is safe.

Stomach and Intestinal problems (gastrointestinal toxicity). Velcade treatment can cause nausea, vomiting, diarrhea, and constipation. If your symptoms are severe, your doctor may recommend IV fluids and/or medications.

Low platelet counts (thrombocytopenia). Velcade can cause low levels of platelets (clot-forming cells). If platelets become very low, there is an increased risk of bleeding. Your doctor may recommend a platelet transfusion or other supportive care.

Lowered white blood cells (neutropenia). Velcade can cause low levels of neutrophils which are a type of white blood cells that help to fight infections. If your white blood cells become low, you can be at higher risk for infections. Tell your doctor if you develop a fever or believe you have an infection.
You will have regular blood tests to check your cell counts during your treatment with Velcade. If the number of these cells is very low, your doctor may change the dose and/or schedule of Velcade.

Tumor Lysis Syndrome (TLS). TLS is a syndrome that causes a chemical imbalance in the blood that could lead to heart and/or kidney problems. TLS can occur with cancer treatments, and your doctor will be monitoring your blood and urine for any signs of this syndrome. If you develop TLS, your doctor will take appropriate steps to treat it.

Liver problems (hepatic toxicity). If you have liver problems, it can be harder for your body to get rid of Velcade. Velcade has caused sudden liver failure in people who were taking many medications or had other serious medical conditions. Symptoms of liver problems include a yellow discoloration of the eyes and skin (jaundice) and changes in liver enzymes measured in blood tests. Your doctor will closely monitor you if you have liver disease. It is not known whether restarting Velcade therapy in patients previously experiencing this complication is safe.

Hematologic disease (Thrombotic Microangiopathy, TMA). Velcade can lead to the formation of blood clots in small blood vessels. These clots can result in low platelets, kidney damage, confusion, and an increased risk of bleeding. Tell your doctor if you develop pinpoint-sized purple dots (petechiae), larger bruises, or you see blood in your urine. Your doctor may stop treatment with Velcade. It is not known whether restarting VELCADE therapy in patients previously experiencing this complication is safe.

Additional Information

#AskDrDurie: Is it okay to take vitamin B12 on the same day as Velcade?

In this video, Dr. Brian G.M. Durie answers a patient’s question about taking a supplement like vitamin B12 on the same day as Velcade.

Understanding Velcade as a Subcutaneous (SQ) injection videos





VELCADE® Treatment Approaches

A Report of Findings from the 2013 Nurse Leadership Board Roundtable Meeting

The VELCADE® website

Information for patients and clinicians on indications and usage

Patient Assistance

VELCADE® downloadable resources

As someone living with multiple myeloma or relapsed mantle cell lymphoma—or as someone caring for a person with one of these diseases—you may have many questions about the disease and its treatment. Our dedicated case managers at 1-866-VELCADE(835-2233), option 2 can provide you and your loved ones with day-to-day and long-term support.



The International Myeloma Foundation medical and editorial content team

Comprised of leading medical researchers, hematologists, oncologists, oncology-certified nurses, medical editors, and medical journalists, our team has extensive knowledge of the multiple myeloma treatment and care landscape. Additionally, Dr. Brian G.M. Durie reviews and approves all medical content on this website. 

Last Medical Content Review: September 27, 2021

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