Chemotherapy kills cells that divide rapidly, such as cancer cells, but the drugs can also harm normal cells that divide rapidly, including bone marrow cells, the cells in hair roots, mucosal cells and skin cells.
Chemotherapy drugs used to treat multiple myeloma may include melphalan, cyclophosphamide, doxorubicin, cisplatin, etoposide and bendamustine.
Typical side effects include a weakened immune system and greater risk of infection, as well as hair loss, mucositis (inflammation of the smooth mucosal tissue inside the mouth and other areas of the body), diarrhea, nausea and rash.
High-dose chemotherapy may be an option for some patients. It is more effective than conventional chemotherapy (which is given in lower doses), but it damages the bone marrow, which produces new blood cells. To overcome that problem, your own (autologous) blood stem cells can be collected in advance, stored in a freezer, and given back to you after the high-dose chemotherapy has destroyed most of the cancer cells in your system.
When this technique was first developed, the bone marrow itself was collected and later reinfused (given back to the patient), but today stem cells can be stimulated to multiply in the bone marrow until they enter the bloodstream, where they can be collected through a process very much like donating blood.
Nuclear export inhibitor
One type of chemotherapy, selinexor (XPOVIO™), is an oral therapy (pill) approved by the FDA in July 2019 for eligible multiple myeloma patients who have exhausted all other treatment options. Specifically, it is for adult patients whose disease has returned after treatment or no longer responds to therapy after at least four previous treatments.
XPOVIO is a nuclear export inhibitor. Here’s how it works: In someone who is healthy, tumor suppressor proteins can prevent cancer from developing. But cancer cells have a way to prevent this. Tumor suppressor proteins must be inside the nucleus of a cell in order to work, so the cancer cells begin to produce large amounts of a protein called Exportin 1 (XPO1), which pulls the tumor suppressor proteins out of the cell nucleus. XPO1 also prevents some of the cell’s other anti-cancer processes from working.
XPOVIO weakens XPO1 to keep it from removing tumor suppressor genes from the nucleus of the cell.
XPOVIO is given along with dexamethasone, an anti-inflammatory drug that works like cortisone.
Proteasome inhibitors block the abnormal proteins or enzymes that stimulate the growth of myeloma cells. Examples of these drugs include bortezomib, carfilzomib and ixazomib. These are usually used in combination with other drugs.
Typical side effects include neuropathy, which causes tingling, numbness or pain in the fingers and toes; diarrhea; orthostasis (dizziness when getting up too fast); and, very rarely, heart failure or difficulty breathing.
Immunomodulatory Drugs (iMiDs)
Immunomodulatory Drugs (IMiDs) activate the immune system to fight cancer. Usually the immune system recognizes that a cell is cancerous and kills it, but sometimes cells can escape. Immunomodulatory drugs reactivate specific parts of the immune system to effectively destroy those cells. IMiDs may include lenalidomide, pomalidomide or thalidomide.
Typical side effects include increased risk of infection, blood clotting, diarrhea or constipation, fatigue, kidney problems and rash.
Antibodies are genetically engineered to zoom in on proteins that are found on the surface of cancer cells and destroy them. Daratumumab and elotuzumab are antibodies.
Typical side effects include allergic reaction and increased risk of infection.
Histone Deacetylase (HDAC) inhibitors
HDAC inhibitors help overcome resistance to other drugs. They block pathways other than those blocked by proteasome inhibitors and help activate tumor suppressor genes in the cell. Panobinostat is an HDAC-inhibitor approved for the treatment of multiple myeloma.
Typical side effects include a weakened immune system, diarrhea, fatigue and nausea.
Steroids can trigger the death of multiple myeloma cells and are part of nearly every combination treatment. Prednisone and dexamethasone are two types of steroids.
Typical side effects increased risk of infection, sleeplessness and facial flushing.