Proteasome inhibitors for multiple myeloma
Fact-checked by Proteasome inhibitors (PIs) are a major class of therapies used to treat multiple myeloma.
Multiple myeloma, often called myeloma, is a rare blood cancer that develops when plasma cells — a type of immune cell that produces antibodies — become abnormal and multiply uncontrollably in the bone marrow.
PIs are used at many stages of myeloma treatment. They may be part of initial (first-line) therapy for newly diagnosed patients, given before and after a stem cell transplant, or used in people whose cancer has returned or stopped responding to earlier treatment (relapsed or refractory disease). Most people with myeloma receive at least one PI during their care.
These medications are often combined with other myeloma treatments, though in some cases they may be used alone.
What are proteasome inhibitors?
Proteasomes are structures inside cells that break down damaged or unneeded proteins and recycle their building blocks. All cells rely on proteasomes, but they are especially important in myeloma cells, which grow quickly and produce large amounts of abnormal proteins.
PIs work by blocking this protein breakdown process. As a result, unwanted proteins build up inside cancer cells, creating stress that can lead to myeloma cell death. These medications may also interfere with certain signaling pathways that help cancer cells survive.
Healthy cells are generally better able to tolerate proteasome inhibition because they produce fewer abnormal proteins than myeloma cells.
Proteasome inhibitors for multiple myeloma
There are three PIs approved in the U.S. to treat adults with myeloma:
- Kyprolis (carfilzomib): used alone or as part of combination regimens for people with relapsed or refractory myeloma; also available as generics
- Ninlaro (ixazomib): used as part of a combination regimen for people who have received at least one prior therapy
- Velcade (bortezomib): used in various treatment regimens for both newly diagnosed and relapsed/refractory myeloma, sometimes given alone and sometimes with other medications; also available as generics
Kyprolis is given as an intravenous (into-the-vein) infusion. Ninlaro is taken as an oral capsule. Velcade may be given either intravenously or as a subcutaneous (under-the-skin) injection.
How often these medications are given depends on the specific treatment plan, but they are typically administered on scheduled days within repeating treatment cycles.
Side effects
Side effects of PIs vary depending on the specific medication and treatment regimen, but may include:
- nausea, vomiting, diarrhea, or constipation
- fatigue or weakness
- low blood cell counts
- symptoms of nerve damage, such as numbness, tingling, or pain in the hands and feet
- swelling
- rash
All approved PIs for myeloma carry a warning for a rare but serious condition called thrombotic microangiopathy, in which clots form in small blood vessels.
Depending on the specific medication, there may also be risks involving the heart, lungs, liver, or kidneys. Doctors monitor patients closely during treatment. Patients should talk with their healthcare team about what to expect with their specific therapy.
PIs may cause fetal harm and should be avoided during pregnancy.
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