What Are the Three Stages of Multiple Myeloma?

Multiple myeloma may not always cause symptoms. When symptoms of multiple myeloma occur, they may include:

• Bone problems
  • Bone pain, often in the back, hips, and skull
  • Bone weakness all over (osteoporosis) or where there is a plasmacytoma
  • Broken bones 
• Low blood counts of red blood cells (anemia), white blood cells (leukopenia), or plasma cells (thrombocytopenia)
• High blood levels of calcium (hypercalcemia)
  • Extreme thirst, leading to drinking a lot
  • Increased urination
  • Dehydration
  • Kidney problems and kidney failure
  • Severe constipation
  • Abdominal pain
  • Loss of appetite
  • Weakness
  • Drowsiness
  • Confusion
  • Coma (when calcium levels are very high)
• Nervous system symptoms if the bones in the spine weaken and cause spinal cord compression
  • Spinal cord compression is a medical emergency. See a doctor right away if you experience: 
    • Sudden severe back pain
    • Numbness, most often in the legs
    • Muscle weakness, most often in the legs
• Nerve damage 
  • Weakness
  • Numbness 
  • “Pins and needles” sensation
• Thickened blood (hyperviscosity) that slows blood flow to the brain
  • Confusion
  • Dizziness
  • Stroke symptoms, such as weakness on one side of the body and slurred speech
  • Nosebleeds
• Kidney problems
  • Weakness
  • Shortness of breath
  • Itching
  • Leg swelling
• Infections, such as pneumonia

The cause of multiple myeloma is not known, though it is believed it may result from genetic changes (mutations). 

Risk factors that may increase the chance of developing multiple myeloma include:

• Age: Most people diagnosed with multiple myeloma are at least 65 years old
• Gender: Men are slightly more likely than women to develop multiple myeloma 
• Race: It is more than twice as common in African Americans than in white Americans
• Family history
• Obesity
• Having other plasma cell diseases
  • Monoclonal gammopathy of undetermined significance (MGUS)
  • Solitary plasmacytoma 

In addition to a patient history and physical examination, multiple myeloma is diagnosed with a combination of blood tests, urine testing, and imaging tests. 

Lab tests used to diagnose multiple myeloma include: 

• Blood tests
  • Complete blood count (CBC) 
  • Blood chemistry 
  • Levels of blood creatinine, albumin, calcium, and other electrolytes
  • Lactic dehydrogenase (LDH) levels 
  • Quantitative immunoglobulins
  • Electrophoresis
  • Serum free light chains
  • Beta-2 microglobulin
• Urine tests 
• Biopsies
  • Bone marrow biopsy
  • Fine needle aspiration biopsy
  • Core needle biopsy
• Imaging tests
  • Bone X-rays
  • Computed tomography (CT) scan
  • Magnetic resonance imaging (MRI) scans
  • Positron emission tomography (PET) scans
  • Echocardiogram (“echo”) of the heart

A diagnosis of multiple myeloma requires:

1. A plasma cell tumor (proven by biopsy) OR at least 10% plasma cells in the bone marrow, AND
2. At least one of the following:

• High blood calcium level
• Poor kidney function
• Low red blood cell counts (anemia)
• Holes in the bones from tumor found on imaging studies 
• Increase in one type of light chain in the blood so that one type is 100 times more common than the other
• 60% or more plasma cells in the bone marrow

There are numerous treatments for multiple myeloma. Treatment may be local (directed at the tumor without affecting the entire body) or systemic. 

Local treatments for multiple myeloma are often used to treat earlier stage cancer, though they are sometimes used in other situations, and may include: 

• Surgery 
  • May be used to remove single plasmacytomas (rarely used to treat multiple myeloma)
  • May also be used when spinal cord compression causes paralysis, severe muscle weakness, or numbness
  • Metal rods or plates may be surgically attached to help support weakened bones and or to prevent or treat fractures
• Radiation therapy
  • May be used to treat areas of bone damaged by myeloma that have not responded to chemotherapy and/or other drugs 
  • The type of radiation therapy most often used to treat multiple myeloma is external beam radiation therapy

Systemic treatments for multiple myeloma reach cancer cells throughout the body and may include: 

• Drug therapy 
  • Although a single drug may be used to treat multiple myeloma, it is preferable to use at least 2 or 3 different kinds of drugs in combination because the cancer responds better
  • Chemotherapy
    • Cyclophosphamide (Cytoxan)
    • Etoposide (VP-16)
    • Doxorubicin (Adriamycin)
    • Liposomal doxorubicin (Doxil)
    • Melphalan
    • Melphalan flufenamide, also known as melflufen (Pepaxto)
    • Bendamustine (Treanda)
  • Corticosteroids (steroids) such as dexamethasone and prednisone
    • May be used alone or combined with other drugs 
    • Also used to help decrease nausea and vomiting caused by chemo 
  • Immunomodulating agents 
    • Thalidomide (Thalomid) 
    • Lenalidomide (Revlimid) 
    • Pomalidomide (Pomalyst) 
  • Proteasome inhibitors 
    • Bortezomib (Velcade) 
    • Carfilzomib (Kyprolis) 
    • Ixazomib (Ninlaro) 
  • Histone deacetylase (HDAC) inhibitors 
    • Panobinostat (Farydak)
  • Monoclonal antibodies 
    • Daratumumab (Darzalex) or a newer form of the drug, called daratumumab and hyaluronidase (Darzalex Faspro)
    • Isatuximab (Sarclisa) 
    • Elotuzumab (Empliciti) 
  • Antibody-drug conjugates 
    • Belantamab mafodotin-blmf (Blenrep) 
  • Nuclear export inhibitor 
    • Selinexor (Xpovio)
  • Bisphosphonates for bone disease
    • Pamidronate (Aredia)
    • Zoledronic acid (Zometa) 
    • Denosumab (Xgeva, Prolia)
  • Stem cell transplant 
  • Chimeric antigen receptor (CAR) T-cell therapy (a type of immunotherapy)
  • Supportive treatments 
    • Intravenous immunoglobulin (IVIG) to help prevent infections
    • Treatment for low blood cell counts
      • Epoetin (Procrit) 
      • Darbepoetin (Aranesp) 
    • Plasmapheresis is used to remove myeloma protein from the blood