Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor 1/2020
The treatment of multiple myeloma is focused on treating the underlying disease (the increased number of abnormal plasma cells). Managing the symptoms and other medical problems resulting from the increased numbers of plasma cells and abnormal (monoclonal) proteins is equally important. Several complications that result from multiple myeloma have specific treatments available.
In 70% of multiple myeloma cases, the bones develop multiple holes, which explains why the disease is referred to as “multiple” myeloma. The holes are referred to as osteolytic lesions, which cause the bones to be fragile and subject to fractures. Osteolytic lesions are caused by the rapid growth of myeloma cells, which push aside normal bone-forming cells, preventing them from repairing general wear and tear of the bones. Under normal circumstances, cells called osteoclasts destroy dead and dying bone. Multiple myeloma causes the secretion of osteoclast-activating factor, a substance that stimulates osteoclasts.
Multiple myeloma involving the bone can cause pain, fracture and other significant problems for patients. Management of bone involvement is an integral part of the overall treatment strategy for multiple myeloma. The first objective of treatment of bone complications is to prevent new bone disease from developing or progression from existing bone lesions to occur.
Bisphosphonate drugs can effectively prevent loss of bone that occurs from metastatic lesions, reduce the risk of fractures, and decrease pain. Bisphosphonate drugs work by inhibiting bone resorption, or breakdown. Bone is constantly being “remodeled” by two types of cells: osteoclasts, which break down bone; and osteoblasts, which rebuild bone. Although the exact process by which bisphosphonates work is not completely understood, it is thought that bisphosphonates inhibit osteoclasts and induce apoptosis (cell death) in these cells, thereby reducing bone loss. There is also evidence that these drugs bind to bone, thereby blocking osteoclasts from breaking down bone.
Bisphosphonate drugs that are FDA-approved for the treatment of cancer-related skeletal complications include Zometa® (zoledronic acid) and Aredia® (pamidronate). Of these two drugs, Zometa appears to demonstrate the strongest activity. An added benefit of Zometa is that it is administered in a dose ten times lower than Aredia, which considerably reduces the administration time from several hours to 15 minutes, resulting in a more convenient regimen for patients. (1,2)
Xgeva prevents bone complications and can delay the time to myeloma progression
The US Food and Drug Administration has expanded the approval of Xgeva (denosumab) for the prevention of skeletal-related events in patients with bone metastasis from multiple myeloma. (3)
Xgeva is different that a bisphosphonate - it targets a protein known as the RANK ligand. This protein regulates the activity of osteoclasts (cells that break down bone). Xgeva has been approved for the treatment of postmenopausal osteoporosis and for the management of bone metastases and treatment-related bone loss. Xgeva, unlike Zometa is not cleared through the kidneys and therefor offers multiple myeloma patients bone protection with a convenient subcutaneous administration.
The FDA approval of Xgeva was based on data from a comparative clinical trial in which 1718 patients were treated with either Xgeva or Zometa and directly compared. Results of the study showed that Xgeva was non-inferior to Zometa in delaying the time to development of bone complications in patients with multiple myeloma. The median time to the first bone complication was similar between the treatments however the median progression-free survival was 10.7 month higher for the Xgeva treated patients who also experienced a trend in improved overall survival. (3)
Xgeva replaced Zometa as the standard of care for patients with multiple myeloma since it was approved. Xgeva is equally effective at delaying bone complications and may delay the time to myeloma progression and represents a better treatment option for individuals with impaired kidney function.
Patients with progressive bone involvement from multiple myeloma may experience worsening pain and/or fracture of the bone from the progressive cancer. Low-dose radiation therapy, as well as analgesics, can help control the pain from bone progression of multiple myeloma.
To learn more about bone complications and bone health, go to
Many multiple myeloma patients develop hypercalcemia, which is an increased level of calcium in the bloodstream. Hypercalcemia results from the destruction of bone from osteolytic lesions or sometimes from the development of generalized osteoporosis, in which all the bones are soft and porous and have lost calcium. Hypercalcemia in patients with multiple myeloma causes fatigue, lethargy and other symptoms. Severe hypercalcemia is a medical emergency requiring immediate treatment. Typically, hypercalcemia is treated with bisphosphonates and hydration.
Decreased Blood Cell Production
The multiplication of the plasma cells in the bone marrow eventually crowds out and suppresses the normal production of blood cells. This may cause a significant decrease in red blood cells, causing anemia; in platelets, causing abnormal bleeding and in white blood cells, causing neutropenia.
Anemia: Anemia, or a decrease in the red blood cell hemoglobin concentration necessary for the transport of oxygen to the body’s organs, is a common complication of multiple myeloma. Anemia may cause patients to experience tiredness, fatigue, shortness of breath and/or a reduced tolerance to activity. Anemia resulting from multiple myeloma can often be treated with erythropoietin. In order to learn more, go to Anemia.
Infections: The depletion of normal white blood cells compromises the patient’s immunity in several ways. First, the number of monocytes and granulocytes are greatly reduced so that the patient is at risk from infections. Second, the delicate and complex balance between the different types of lymphocytes is distorted. Patients with multiple myeloma often have reduced levels of normal immunoglobulin necessary to fight certain types of infections. Patients experiencing recurrent infections may need to have immunoglobulin levels replenished. Patients who experience recurrent infections may want to ask their physician about immunoglobulin replacement therapy.
In 75% of patients, the plasma cells also produce monoclonal incomplete immunoglobulins, called light chains. These are excreted in the urine and are the so-called Bence Jones proteins. Bence Jones proteins are named after a British physician, Henry Bence Jones (1813-1873), who first discovered them. Bence Jones proteins may deposit in the kidney, clogging the tubules. Ultimately, this damages the kidney and can cause renal failure. Hypercalcemia may exacerbate kidney problems because excess calcium in the bloodstream causes excessive fluid loss and dehydration. Because the abnormal proteins produced by the plasma cells are eliminated from the body through the urine, they may accumulate in the kidneys and cause kidney dysfunction. In addition to treating the underlying cancer, it is important for patients to maintain adequate oral intake of fluids to help avoid kidney failure and avoid using over-the-counter medications such as non-steroidal anti-inflammatory drugs that can worsen kidney function.
- Berenson JR, Lichtenstein A, Porter L et al. Long-term pamidronate treatment for advanced multiple myeloma patients reduces skeletal events. Journal of Clinical Oncology. 1998;16:593-602.
- Rosen LS, Gordon D, Kaminski M et al. Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma. Cancer. 2003;98:1735-1744.
- Denosumab More Effective Than Zometa at Delaying Bone Complications