What Are Proteasome Inhibitors?

An Emerging Class of Drug Used to Treat Systemic Cancers

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An emerging treatment for cancers affecting the blood and immune system, such as multiple myeloma (MM) and lymphoma, proteasome inhibitors are pharmaceutical drugs that work by inhibiting protein function.

This class of medication stops the activity of proteasome, a protein associated with digesting unusable cellular waste products, which in turn can kill the cancer cells. Often used in conjunction with other medications, there are three such drugs currently employed: Velcade (bortezomib), Krypolis (carfilzomib), and Ninlaro (ixazomib).

Multiple myeloma patients are usually delivered these drugs intravenously or via injection as part of their treatment plan, though a newer, oral form of this medication is now available. Like other cancer therapies, proteasome inhibitors do come with an array of side-effects, and some patients aren’t a good fit for this class of medication.

These drugs are emerging as an effective means of stopping the spread of cancer or preventing relapse. As such, it’s important for people with lymphoma, MM, or other blood cancers to understand the basics of these treatments.

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Dosage

Proteasome inhibitors target and block the function proteasome, leading to a lethal build-up of waste products in multiple myeloma cells. For most types of this drug, either a syringe or an IV is used to deliver these medications in most cases, dosing occurs in the clinic and is carefully managed by the doctor.

However, newer, oral versions of proteasome inhibitors, taken at home, are now also on the market. Though there are variations, the courses of treatment with these drugs are sketched out below.

Velcade (bortezomib)

Velcade (bortezomib) is usually be administered via IV or abdominal injection and tends to be attempted after other therapies or drugs haven’t yielded results in MM or lymphoma cases.

Treatment is combined with prednisone (an anti-inflammatory drug) and the chemotherapy drug melphalan and lasts six weeks; there are two weekly doses in the first month, and then one a week for the rest of the time.

For lymphoma, two injections a week are delivered for two weeks alongside a number of chemotherapy drugs, followed by a rest period.

Krypolis (carfilzomib)

This medication is indicated only for MM and is delivered using an IV. The cycle of treatment is 28 days, with patients receiving two doses a week for the first three weeks, followed by a 12-day rest period.

Depending on the progression of the cancer, treatment can be taken up for multiple courses, with specific dosages adjusted as necessary.

Ninlaro (ixazomib)

This is an oral proteasome inhibitor that’s taken in 4-milligram (mg) doses once a week for the first three weeks of a 28-day cycle (on days one, eight, and 15). The timing of dosing should be consistent, and the pill needs to be taken one hour before, or at least two hours after meals or food.

Like the others, it’s usually administered alongside other drugs and is attempted when previous therapies haven’t yielded results.    

Precautions

It’s important to remember that treatment for cancer—especially more difficult types like MM and lymphoma—tends to be an evolving process. Therapy with proteasome inhibitors is one of multiple options, and the best course of action depends on a number of factors.

In addition to conditions that outright contraindicate their use, there are others that can also impact decision-making. What do doctors look out for? Here’s a quick breakdown:

  • Allergy to certain drugs, such as bortezomib or boron, is a contraindication.
  • Pregnancy is contraindicated as the fetus can get hurt by these medications.
  • Breastfeeding is considered unsafe during treatment.
  • Heart disease or a history of heart problems should be considered before use.
  • Lung problems, including lung disease or breathing problems, are considerations.
  • Liver disease, which impacts the body’s ability to process drugs, might impact the decision to use these drugs.
  • Kidney disease increases the risk of serious complications.
  • Nerve problems can become worse with treatment.
  • Low platelet count, leading to an inability for blood to clot, could be a contraindication to treatment with these drugs.
  • Hormonal birth control, such as Nuva rings, implants, or injections, if taken with some other drugs, should be assessed before using these medications.
  • Dehydration prior to treatment may need to be corrected before using these drugs.

When consulting with your doctor, make sure to provide as much information as possible about your health and prescription history.

Side Effects

Proteasome inhibitors, like most cancer drugs, do cause a wide range of side-effects, many of which need to be medically managed. The course of treatment is therefore one of careful observation and monitoring. Though these may vary depending on the specific drug taken, common side-effects include:

  • Nausea
  • Vomiting
  • Diarrhea
  • Constipation
  • Anemia
  • Low white blood cell count
  • Difficulty urinating
  • Rash
  • Loss of appetite
  • Agitations and confusion
  • Bloody stools
  • Numbness and tingling in the limbs
  • Weight gain
  • Bloating in arms, face, or legs
  • Bleeding gums
  • Difficulty breathing
  • Chest pain
  • Fatigue
  • Disrupted heartbeat
  • Back pain

Generally speaking, let your doctor know if you’re experiencing any of the above. In addition, there are a couple of rarer and more serious adverse effects:

  • Chills
  • Fever
  • Heart failure
  • Pulmonary edema (fluid in the lungs)
  • Muscle cramps and pain
  • Blisters on the body
  • Limb weakness

Throughout proteasome therapy, your doctors will do what they can to take on these side-effects; however, patients need to be vigilant and let them know if these are arising.  

A Word From Verywell

There’s no denying that cancers, especially systemic cancers like lymphoma or MM, are tremendously difficult to take on. Beyond the health effects of the conditions, themselves, treatment, too, can take a huge toll on the body.

That said, new and emerging therapies, such as those employing proteasome inhibitors, are boosting the doctor’s toolkit and improving prognoses for patients. As drugs like these continue to be employed, and as further applications are found for them, the outlook for cancer patients will continue to get better.

Managing cancer is a long and difficult road; however, with the help of emerging drugs like proteasome inhibitors, it’s easier than ever before to undertake. 

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Article Sources
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  2. Multiple Myeloma Research Foundation. Proteasome inhibitors. Published 2017. 

  3. MedlinePlus. Ixazomib. Updated February 15, 2016.

  4. MedlinePlus. Bortezomib. Updated November 15, 2019.

  5. MedlinePlus. Carfilzomib injection. Updated August 15, 2020.