Managing Skeletal-Related Events in Multiple Myeloma Patients

Multiple myeloma is a cancer of the plasma cells. Plasma cells are a type of white blood cell found in the bone marrow and are part of the immune system. When these cells become cancerous and multiply uncontrollably, it results in a diagnosis of multiple myeloma. When these cancerous cells proliferate, it crowds out healthy blood cells in the bones, and instead of producing antibodies the body needs, they create harmful proteins. These proteins break down bone, causing bone pain, increased risk of fractures, and increased risk of skeletal-related events.

Treatment for multiple myeloma can include targeted therapy, biological therapy, chemotherapy, corticosteroids, chemotherapy, radiation therapy, and/or bone marrow transplant. Each person’s course of treatment can vary, and different treatments may be used at different times. Treatment can depend on a variety of factors, including stage of disease, type of multiple myeloma, your age, and other health factors or conditions.

With survival outcomes improving for multiple myeloma and individuals living for longer periods of time with the condition, it’s important to have treatments that help keep bones strong and reduce the risk of skeletal-related events.

What are skeletal-related events?

Skeletal-related events (SREs) are complications that are typically related to bone metastases, or the spread of cancer, and can include fractures, spinal cord compression, pain, and hypercalcemia.¹ They can also contribute to lower quality of life, depression, reduced independence, and decreased mobility.

What is myeloma-related bone disease?

One of the main features of multiple myeloma is osteolytic bone disease. This bone disease results in overproduction of osteoclasts, which absorb bone tissue, and suppression of osteoblasts, which help to build bone. This results in dramatic bone loss, in turn, affecting quality of life and eventually, increases morbidity and mortality. According to Terpos et al (2018), up to 80% of multiple myeloma patients present with osteolytic bone lesions at diagnosis, which increases their risk of a serious skeletal-related event.² Up to 60% of patients with myeloma will experience a fracture.² Bone disease and SREs, then, are important to address when discussing treatment of myeloma because not only do these impact health and survival, but perhaps even more importantly, they affect quality of life for an individual living with multiple myeloma.

Treatments for multiple myeloma-induced bone disease

The treatment for multiple myeloma-induced bone disease is multi-pronged: bisphosphonates and targeted therapies, orthopedic interventions, local radiation, and palliative treatments. Bisphosphonates are a first-line treatment for myeloma-related bone disease. They bind to bone structures and help reduce the activity of osteoclasts. They don’t promote new bone growth or foster repair of lesions, though. They also have significant side effects, including renal toxicity and GI upset. Targeted therapies have shown promise, but also have the potential to have serious adverse effects, and may not be right for everyone. Local radiation can be used to help relieve pain, along with analgesic medications. It’s important, though, not to irradiate too much so as to further weaken bone.

In early 2018, the Food and Drug Administration (FDA) approved denosumab (brand name Xgeva) to help prevent SREs in patients with multiple myeloma. Denosumab is a RANK ligand (also called RANKL) inhibitor. This medication inhibits the protein RANKL, helping to decrease bone resorption and loss, and helps to increase bone strength.³ Especially for individuals with kidney issues, this new drug is especially helpful, since unlike bisphosphonates, it is not cleared by the kidneys.⁴ This is important, since reduced kidney function is often a complication of multiple myeloma, from the excess calcium in the bones interfering with kidney function. The most common side effects of denosumab were fatigue, anemia, low levels of phosphorus in the blood, and muscle weakness.

When used in conjunction with other treatments, this new drug has the potential to improve treatment outcomes and quality of life for patients living with multiple myeloma. If it’s something you’re interested in, talk with your doctor to see if it might be an option for you.