Proteasome inhibitors are a mainstay of multiple myeloma treatment. Since their introduction more than a decade ago, they have greatly improved the outlook for people with multiple myeloma.

Drug therapy is an important part of multiple myeloma (MM) treatment.

Proteasome inhibitors (PIs) have been the backbone of MM treatment for the past decade. They may be used during different phases of disease progression, often in combination with other drugs.

The availability of PIs has greatly improved outcomes in people with MM. Researchers continue to develop and evaluate new PIs in both preclinical and clinical settings.

Fast facts about multiple myeloma

  • The average 5-year survival rate for MM is 59.8%.

Proteasomes are large protein complexes that work to break down unneeded or misfolded proteins within a cell. PIs work to block the activity of proteasomes.

When the proteasome isn’t working as it should, excess proteins begin to build up in the cell. This eventually causes your cell to die.

Cancer cells, such as those in MM, are more responsive to PIs than healthy cells. This is because cancer cells grow and divide more rapidly, meaning they have a higher rate of both protein synthesis and disposal.

The PIs that are currently approved by the Food and Drug Administration (FDA) to treat MM are:

New and upcoming proteasome inhibitors for multiple myeloma

Along with the currently approved PIs, researchers are hard at work researching new PIs to be used in the treatment of MM.

Some examples of PIs with promising early results are marizomib and oprozomib. Both drugs have the potential to be given orally (by mouth). Marizomib can also be given via intravenous (IV) injection or infusion.

Very early trial results of an oral PI called TQB3602 have also been positive. You can find more clinical trials involving current and upcoming PIs here.

When you first receive a diagnosis of MM, PIs are typically used as a part of an initial combination drug treatment. This is typically a combination treatment called VRd that includes:

Bortezomib may also be used along with lenalidomide as maintenance therapy in people whose MM is high risk. People with high-risk MM tend to have more aggressive disease and a poorer outlook.

Maintenance therapy is treatment that you may have after your initial therapy ends. It aims to keep you in remission and prevent progression of your MM.

Carfilzomib is used when your MM has come back or other drugs haven’t worked to manage your MM. It can be given as a single drug or in combination with dexamethasone and possibly lenalidomide.

Ixazomib may also be used when other drugs haven’t been effective. It’s given in combination with lenalidomide and dexamethasone.

How you receive PIs for your MM will depend on which PI you’re prescribed.

Bortezomib (Velcade)

You can receive bortezomib in two ways. It can be given as an injection under your skin (subcutaneous), or it can be directly infused into a vein (intravenous).

Like many cancer drugs, bortezomib is given in cycles. This is a period of treatment followed by a rest period. The rest period gives your body time to recover. During treatment, you may receive bortezomib once or twice a week.

The exact number of cycles of bortezomib used in your initial treatment can vary. A 2022 article recommends up to 12 cycles of VRd, depending on your MM risk level and whether or not you’re getting a stem cell transplant.

Bortezomib is also used for maintenance therapy. Generally speaking, maintenance therapy is given until your MM progresses. It’s discontinued for some people due to side effects.

Carfilzomib (Kyprolis)

Carfilzomib is given intravenously once or twice weekly. The prescribing information notes that it can be continued until your MM progresses or unacceptable side effects occur.

Ixazomib (Ninlaro)

Ixazomib is taken by mouth as a capsule. You typically take it once a week for 3 weeks and then take a week off.

As with carfilzomib, the prescribing information for ixazomib notes that you can take it until your MM progresses or you have unacceptable side effects.

Bortezomib was the first PI approved by the FDA in 2003. Over time, the introduction of PIs and other newer MM treatments have led to an improved outlook for people with MM.

A 2019 study found bortezomib to be an effective treatment option that increased median overall survival for people with relapsed or refractory MM.

A 2023 phase III trial found that the combination of daratumumab, bortezomib, and dexamethason for treatment of relapsed or refractory myeloma significantly prolonged overall, progression-free survival.

The main benefit of PIs is improving the outlook for people with MM. Some PIs also have added benefits.

For example, bortezomib can be very beneficial for people with MM and kidney problems. Further, ixazomib is taken by mouth and can be helpful for people who have trouble going into their doctor’s office for regular injections or infusions.

But PIs can also have a variety of unpleasant side effects. These vary by drug.

Bortezomib (Velcade)

The most common side effects of bortezomib are:

Carfilzomib (Kyprolis)

The common side effects of carfilzomib are:

Ixazomib (Ninlaro)

The most common side effects of ixazomib include:

Along with PIs, there are other treatments that are available for MM. These include:

PIs are drugs that are used to treat MM. Their introduction greatly improved the outlook for people with MM. As such, they’re currently the backbone of MM therapy.

You can receive PIs as a part of your initial therapy or as a component of maintenance therapy. PIs may also be used if your MM relapses or doesn’t respond to other drugs.

While PIs have many benefits for people with MM, they can also have a variety of side effects. If you’ve received a diagnosis of MM, talk with a doctor about the potential side effects of PIs before starting treatment.