Velcade (bortezomib)

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 (bortezomib) is approved by the FDA for use throughout the myeloma disease course, in combination with nearly all other FDA-approved anti-myeloma therapies. Velcade has demonstrated the ability to produce a beneficial effect even in patients who were already treated with Velcade in a prior line of therapy. 

Velcade is used in the following ways with multiple myeloma:

• as induction therapy for newly diagnosed multiple myeloma (NDMM)
• as part of a conditioning regimen for autologous stem cell transplant (ASCT)
• as consolidation therapy
• as maintenance therapy
• as treatment for patients whose myeloma has relapsed or has become refractory 

 

How Does Velcade Work?

Velcade is in a drug class of proteasome inhibitors, drugs that interfere with the normal function of the proteasome, a joined group (“complex”) of enzymes (“proteases”) that break down the damaged or unwanted proteins in both normal cells and cancer cells 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. This process is important for maintaining balance within the cell and for regulating cell growth. 

When Velcade inhibits proteasome function, myeloma cells stop dividing and stop producing chemicals that stimulate other myeloma cells. Also, the autocrine feedback loop is interrupted. Myeloma cells are more sensitive to these effects than normal cells, so myeloma cells die while normal cells can recover.  

How Is Velcade Given?

In 2003, Velcade received FDA approval for the treatment of patients with progressive disease after previous treatment, to be administered as an intravenous (IV) infusion at a doctor’s office or a clinic. 

In 2012, the FDA granted approval for Velcade to be administered as a subcutaneous (SQ) injection under the skin. The SQ shot of Velcade is given at a doctor’s office or a clinic at the same dose and on the same schedule as the IV method of administration. SQ injections should be given on a sequential rotation of 4 injection sites: the left and right sides of the abdomen and the left and right thighs. It is important to note that there is no data to support administration of SQ Velcade in the arm. 

Data on side effects from clinical trials with Velcade have demonstrated that SQ administration causes significantly less peripheral neuropathy (PN) than IV administration, and may also reduce the occurrence of gastrointestinal (GI) side effects. If you have pre-existing PN or GI problems, you should discuss using SQ Velcade with your doctor. 

What Is the Dose and Schedule for Velcade?

If you have newly diagnosed multiple myeloma (NDMM), discuss with your doctor the most appropriate treatment strategy for your disease. As a newly diagnosed myeloma patient, your decision to undergo Velcade therapy may be affected by the following factors: 

• your personal preference 
• your plans for transplant (or not) 
• the presence or absence of kidney problems or neuropathy 
• whether or not you have high-risk multiple myeloma (HRMM) 
• your insurance coverage and other personal or medical factors. 

 

The DVRD Regimens 

In July 2024, the FDA approved the “quadruplet” (4-drug) DVRd regimen for induction therapy and consolidation therapy in patients with newly diagnosed multiple myeloma (NDMM) who are eligible for autologous stem cell transplant (ASCT). 

The DVRd regimen combines four FDA-approved drugs, each from a different drug class and with a different way of attacking myeloma: monoclonal antibody Darzalex Faspro® (daratumumab + hyaluronidasefihj), proteasome inhibitor Velcade, immunomodulatory agent Revlimid® (lenalidomide), and a steroid (dexamethasone). Each drug in this combination therapy enhances the activity of the other drugs. 

The FDA approval of DVRd is based on data from the PERSEUS phase III clinical trial of DVRd in ASCT-eligible patients with NDMM. A total of 709 myeloma patients were randomized to receive DVRd (355 patients) or VRd (354 patients). Patients were 70 years or younger and had a performance status of 0 to 2 based on the scale by the Eastern Cooperative Oncology Group (ECOG), now part of the ECOG-ACRIN Cancer Research Group. 

The PERSEUS study demonstrated a 60% reduction in risk of disease progression or death. Further, there was a significant advantage in overall MRD-negativity rate between the DVRd study arm (57.5%) and VRd study arm (32.5%). Additionally, the MRD negativity among those who also achieved a complete response (CR) or better was 76.6% (DVRd arm) and 58.5% (VRd arm). 

The Isa-VRd regimen 

In September 2024, the FDA approved the “quadruplet” regimen of monoclonal antibody Sarclisa® (isatuximab, Velcade, Revlimid, and dexamethasone [Isa-VRd] for transplant-ineligible patients with NDMM. 

The FDA approval of Isa-VRd is based on data from the IMROZ phase III clinical trial. This trial compared the efficacy and safety of Isa-VRd vs. VRd for transplant-ineligible patients with NDMM. The study included 446 patients and the primary endpoint was progression-free survival (PFS). The results showed that Isa-VRd reduced the risk of progression or death by 40.4% compared to VRd. Isa-VRd also led to deep and sustained responses, with higher rates of complete response (CR), MRD-negativity, and sustained MRD-negativity for at least 12 months. The safety profile of Isa-VRd was consistent with the addition of Sarclisa to VRd. 

The VRd regimen 

Please note that the “triplet” (3-drug) combination therapy of Velcade,  Revlimid, and dexamethasone [VRd] continues to be used in some regions. 

Velcade in Relapsed Disease Settings 

Therapy with Velcade has been demonstrated to be effective in various combinations and sequences, as well as in the settings of a conditioning regimen, consolidation therapy, maintenance therapy, and relapsed or refractory multiple myeloma (RRMM). 

The XVd regimen 

In 2020, the FDA approved the combination of Xpovio® (selinexor), Velcade, dexamethasone [XVd] for myeloma patients who have received at least 1 prior therapy. The XVd regimen is given once-weekly. The FDA approval of the XVd regimen was based on data from the BOSTON phase III randomized clinical trial. 

The BOSTON clinical trial evaluated the clinical efficacy of XVd compared with Vd in 402 participants (195 in the XVd group and 207 to the Vd group). In the XVd group, the doses of Velcade and dexamethasone were reduced by 40% and 25%, respectively. At the median follow-up of 16.5 months in the Vd group, the PFS was 9.46 months. At the median follow-up of 13.2 months in the XVd group, the statistically significant increase in PFS was 13.93 months. The XVd group outperformed the Vd group not only in PFS but also in the overall response rate (ORR): patients over 65 years old, frail patients, patients with high-risk cytogenetics such as del(17p), patients with moderate renal (kidney) insufficiency, and patients who had previously received Velcade or Revlimid. In addition, peripheral neuropathy was less prevalent in the XVd group than in the Vd group. 

Kidney impairment, chromosomal abnormalities, and VTE 

Several clinical trials have confirmed the safety and efficacy of Velcade for patients with renal (kidney) impairment. Clinical trials with Velcade have also demonstrated its ability to help prevent bone loss in myeloma patients. 

In addition, clinical trials using various treatment strategies incorpo rating Velcade have shown that Velcade can help overcome chromosomal abnormalities, t(4;14) in particular, and significantly improve overall survival. 

There is low risk of venous thromboembolism (VTE) with Velcade, and Velcade may even provide a protective effect against VTE in combination with immunomodulatory agent-based regimens. 

Dose and schedule of Velcade 

Velcade may be administered once-weekly or twice-weekly in combination with other drugs. However, clinical trial data have shown that a once-weekly schedule of Velcade is associated with reduction of side effects without reduction in treatment efficacy when compared to the twice-weekly schedule. 

If you experience side effects, have pre-existing medical conditions, or are elderly or frail, your doctor may choose to lower your dose of Velcade, to change your treatment schedule, or to skip your scheduled dose(s) 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 or 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: If a Grade 3–4 AE (adverse event, or side effect) occurs with the above dosing:

1. discontinue therapy
2. wait for a Grade 1 AE
3. restart at a lower dose

 

Possible side effects of Velcade 

Most of the side effects associated with Velcade are manageable and predictable. The most significant and most frequently occurring side effects are described here. Your doctor can provide more information in greater detail. Be sure to promptly report any changes in your health to your doctor. 

*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.

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.