Recurrent multiple myeloma, also called relapsed multiple myeloma, is a reality that most people with this blood cancer will face at some point during their journey with the disease. While this can feel discouraging, modern treatment options are giving patients more hope and time than ever before, with doctors now able to offer several different approaches to help control the disease when it returns.
Understanding Recurrent Multiple Myeloma
When multiple myeloma returns after treatment, doctors call this a relapse or recurrence. This happens when abnormal plasma cells, which are a type of white blood cell made in the bone marrow, begin to grow again after a period of control or remission. During the course of multiple myeloma, many patients will experience several cycles of remission and relapse, each requiring treatment adjustments to keep the disease under control.[7]
The disease is considered recurrent when there are clear signs that the myeloma has become active again after achieving remission. Doctors identify this through blood or urine tests showing increased levels of abnormal proteins produced by the myeloma cells, or through new symptoms developing. According to the International Myeloma Working Group, relapsed refractory multiple myeloma is defined as progressive disease or poor response despite treatment, including progression within 60 days of the most recent treatment in a patient who had achieved remission.[7]
Understanding what makes relapsed myeloma particularly challenging helps patients and their families prepare for what lies ahead. Patients who fail to achieve at least minimal response on initial therapy and continue to progress while on treatment are termed as having “primary refractory” disease. The disease becomes even more complex when classified as “double refractory,” which means it has progressed during or after treatment with both a proteasome inhibitor and an immunomodulatory agent. When resistance extends to monoclonal antibodies as well, it is considered “triple-class” refractory disease, which indicates a more difficult situation requiring specialized treatment approaches.[7]
How Common Is Recurrent Multiple Myeloma
Recurrent multiple myeloma is unfortunately very common among people diagnosed with this blood cancer. Multiple myeloma is considered an incurable disease, and most patients eventually experience relapse, including those who achieved remission with their initial treatment.[7] Over the course of the disease, most patients will have several cycles of remissions and relapses, necessitating multiple lines of treatment throughout their journey with the condition.[7]
The risk of relapse is something that all multiple myeloma patients face, regardless of how well their initial treatment worked. Even patients who respond very well to their first treatment and achieve what doctors call a complete remission can still experience a return of the disease months or years later. This pattern of relapse is a defining characteristic of multiple myeloma and shapes how doctors approach long-term management of the condition.[9]
What Causes Multiple Myeloma to Return
The exact reasons why multiple myeloma returns after treatment are not fully understood by scientists. However, research has shown that the disease is driven by genetic alterations and mutations in the plasma cells. These changes in the cells’ genetic material, especially involving chromosome 14, play an important role in how the disease develops and behaves.[2]
Multiple myeloma is thought to arise from a pre-cancerous condition called monoclonal gammopathy of undetermined significance, or MGUS, which is a benign phase where abnormal plasma cells grow slowly without causing harm. The cell of origin appears to be a plasma cell that has already been through certain developmental stages in the immune system. While MGUS itself is quite common and usually stable, it has about a 1% risk per year of progressing to active multiple myeloma.[2]
When myeloma returns, it often means that some cancer cells survived the initial treatment and began multiplying again. These surviving cells may have developed resistance to the drugs that were used, or they may have been hiding in parts of the body where the treatment couldn’t reach them effectively. Other genetic changes such as alterations in genes called NRAS, KRAS, and BRAF may also participate in helping the abnormal plasma cells continue to grow and divide.[2]
Risk Factors for Recurrence
Several factors can affect the likelihood and timing of multiple myeloma recurrence. One important consideration is how long the disease stayed in remission after the first treatment. If myeloma returns within 18 months of the initial treatment, it suggests more aggressive disease that may be harder to control. On the other hand, if the remission lasts longer than 18 months, the disease may respond better to subsequent treatments.[10]
The characteristics of the cancer cells themselves also matter. Certain genetic patterns and abnormalities in the myeloma cells can make the disease more likely to come back or more difficult to treat when it does return. Additionally, how well a patient responded to their initial treatment provides important clues about how the disease might behave in the future.[9]
A patient’s overall health and physical condition also plays a role in managing recurrent disease. Being in good physical shape, maintaining a healthy weight, and having no other serious medical conditions can help patients tolerate additional treatments and potentially respond better to therapy. Age is also a consideration, as multiple myeloma predominantly affects older adults, with a median age at diagnosis of about 70 years.[2]
Symptoms of Recurrent Multiple Myeloma
The symptoms that appear when multiple myeloma comes back can vary greatly from person to person. Some patients may notice the same symptoms they had when first diagnosed, while others might experience different problems. In some cases, especially in early relapse, there may be no noticeable symptoms at all, and the return of disease is only detected through routine blood or urine tests.[3]
Bone pain is one of the most common symptoms of recurrent myeloma, particularly affecting the spine, chest, or hips. This happens because the abnormal plasma cells can activate other cells in the bone marrow that damage and weaken the bones, creating painful spots and increasing the risk of fractures. Some patients describe this pain as constant and aching, while others experience sharp pains with movement.[4]
Fatigue and weakness are also frequently reported by patients with recurrent myeloma. This overwhelming tiredness occurs because the cancer cells crowd out the normal cells in the bone marrow that make red blood cells, leading to anemia, which is a condition where you don’t have enough healthy red blood cells to carry oxygen throughout your body. Over 60% of multiple myeloma patients have anemia at the time they are diagnosed, and this can worsen or return when the disease relapses.[4]
Frequent infections can signal that myeloma has returned. When abnormal plasma cells take up too much space in the bone marrow, there’s less room for the white blood cells that fight infections. This makes patients more vulnerable to catching colds, flu, and other illnesses. The infections may be more severe or take longer to clear up than normal.[5]
Other symptoms that might appear include nausea, constipation, loss of appetite, mental fogginess or confusion, weight loss, increased thirst, and needing to urinate more often. Some patients experience weakness in their arms or legs, or notice bruising and bleeding more easily than usual. These varied symptoms reflect the many ways that multiple myeloma can affect different parts of the body.[3][5]
Patients with relapsed myeloma also commonly struggle with ongoing symptoms related to their treatments. Peripheral neuropathy, which is pain, numbness, and tingling in the hands and feet, can be caused by certain drugs used to treat myeloma. Side effects from steroids, which are a mainstay of myeloma treatment, can include weight gain, mood changes, trouble sleeping, and weakening of bones over time. These treatment-related symptoms can significantly impact daily life and quality of living.[16][17]
Preventing Recurrence and Maintaining Health
While there is no guaranteed way to prevent multiple myeloma from coming back, there are steps patients can take to support their overall health and potentially improve their outcomes. Maintaining a healthy lifestyle becomes especially important for people living with this chronic condition, as it can help manage symptoms, reduce treatment side effects, and improve quality of life.[15]
Regular physical activity is one of the most beneficial things patients with recurrent myeloma can do. Exercise helps reduce stress, improve sleep, manage pain, cope with fatigue, strengthen physical function, reduce anxiety, boost self-esteem, and improve overall quality of life. Sports medicine experts recommend that people with cancer aim for at least 30 minutes of moderate aerobic exercise at least three days a week, plus two days of resistance training. However, it’s important to work with your doctor or a physical therapist to create an exercise plan that’s safe for your specific situation, especially if you have bone damage or are experiencing pain.[14][15]
Eating a balanced, nutritious diet is another important component of self-care. While there’s no specific diet proven to prevent myeloma recurrence, eating well can help stabilize energy levels, maintain a healthy weight, and support your body’s ability to tolerate treatments. A diet rich in fruits, vegetables, whole grains, and lean proteins provides the nutrients your body needs to function at its best. Some patients find it helpful to work with a nutritionist who understands the special needs of cancer patients.[14]
Maintaining a healthy weight is particularly important for multiple myeloma patients. Being overweight or having obesity is linked with a higher risk of getting multiple myeloma in the first place, and carrying extra weight may also affect outcomes in people who already have the disease. Weight gain can be a challenge during myeloma treatment because steroids increase appetite and promote fat storage, and pain or fatigue may make it harder to stay active. Working with your healthcare team to manage your weight through appropriate diet and exercise can make a real difference.[2][16]
Getting enough good quality sleep helps your body heal and gives you energy to face each day. Many myeloma patients struggle with sleep problems due to pain, medication side effects, or anxiety. Creating a regular sleep schedule, making your bedroom comfortable and dark, avoiding caffeine late in the day, and practicing relaxation techniques before bed can all help improve sleep quality.[14]
Avoiding tobacco and limiting alcohol consumption are also important. Smoking and excessive drinking can interfere with treatment effectiveness and worsen side effects. If you smoke, talk to your doctor about programs that can help you quit. Alcohol consumption has been identified as a contributing factor to myeloma development, so limiting or avoiding alcohol is a wise choice.[2]
Taking steps to prevent infections is crucial for myeloma patients, whose immune systems are weakened by both the disease and its treatments. This includes washing hands frequently, avoiding crowds during cold and flu season, staying up to date with recommended vaccinations (after checking with your doctor about which vaccines are safe for you), and promptly reporting any signs of infection to your healthcare team.[14]
How Recurrent Multiple Myeloma Affects the Body
When multiple myeloma recurs, the abnormal plasma cells once again begin to accumulate in the bone marrow, which is the soft, spongy tissue at the center of bones where blood cells are made. These cancerous plasma cells grow out of control, crowding out the normal cells that help the body function properly.[4]
As the myeloma cells multiply, they produce an abnormal antibody protein called M protein. This protein is not useful for fighting infections like normal antibodies are. Instead, high levels of M protein are a hallmark characteristic of multiple myeloma and can cause several problems. The protein can build up in the bone marrow and cause the blood to thicken. It can also accumulate in the kidneys and other organs, potentially causing damage. Some patients develop a related condition called amyloidosis, where abnormal proteins build up in tissues and organs.[1][4]
The crowding out of normal blood cells in the bone marrow leads to several complications. With fewer red blood cells being made, patients develop anemia, which causes weakness, fatigue, shortness of breath, and dizziness. A reduction in normal white blood cells means decreased ability to fight infections, leaving patients vulnerable to frequent and potentially serious illnesses. Lower platelet counts can lead to excessive bleeding and easy bruising.[4][5]
The myeloma cells also affect the bones themselves. They activate other cells in the bone marrow that break down bone tissue, causing weakened spots called osteolytic lesions. This bone destruction increases the risk of fractures and can lead to elevated calcium levels in the blood, a condition called hypercalcemia. High calcium levels can cause confusion, constipation, increased thirst, and frequent urination. The bone damage is also responsible for much of the pain that myeloma patients experience.[4][5]
In recurrent disease, these processes repeat as the myeloma cells regain their foothold in the body. The extent and severity of these effects can vary depending on how aggressive the relapse is, how much disease is present, and how quickly it’s detected and treated. This is why regular monitoring through blood tests, urine tests, and sometimes bone marrow biopsies is so important for patients who have been treated for multiple myeloma.[12]
