Plasma Cell Myeloma Refractory

When multiple myeloma stops responding to treatment or never responds at all, doctors call it refractory myeloma. This challenging form of the disease requires new treatment strategies and ongoing monitoring to manage symptoms and slow progression.

Table of contents

• What Is Refractory Multiple Myeloma?
• What Causes Refractory Multiple Myeloma?
• Symptoms of Refractory Multiple Myeloma
• How Is Refractory Multiple Myeloma Diagnosed?
• Treatment Options for Refractory Multiple Myeloma

What Is Refractory Multiple Myeloma?

Multiple myeloma is a type of cancer that affects plasma cells, a kind of white blood cell made in the bone marrow. Normally, plasma cells help your body fight infections by making antibodies. In multiple myeloma, abnormal plasma cells grow out of control and form tumors in the bones or soft tissues^[1].

Refractory multiple myeloma happens when the cancer does not respond to treatment. There are two main types of refractory disease. Primary refractory means the cancer never responded to the first treatment you tried. Your doctor might use this term when you fail to achieve at least minimal response on initial therapy and your disease continues to progress while on treatment^[1].

The term relapsed/refractory multiple myeloma (RRMM) describes cancer that improved at first but then became resistant to treatment and started growing again^[1]. According to the International Myeloma Working Group, this includes progressive disease, poor response despite treatment, or progression within 60 days of the most recent treatment in a patient who had achieved remission^[1].

Multiple myeloma is considered double refractory if the disease has progressed during or after treatment with both a protease inhibitor and an immunomodulatory agent. If the patient is also resistant to monoclonal antibodies, it is considered triple-class refractory disease, which means the outlook is more challenging^[1].

Relapsed and refractory multiple myeloma, RRMM, primary refractory myeloma, plasma cell myeloma

What Causes Refractory Multiple Myeloma?

In multiple myeloma, abnormal plasma cells multiply in your bone marrow, the soft tissue in the center of bones where new blood cells are made^[2]. As these abnormal cells grow and divide, they cause problems in the blood cells and bone marrow^[4].

Researchers do not know exactly what causes multiple myeloma or why it becomes refractory in some people. They believe that gene changes may make the cancer more resistant to treatment^[8]. What leads to the mutations that cause patients to be resistant to first-line treatments remains unknown^[4].

Symptoms of Refractory Multiple Myeloma

The symptoms in refractory multiple myeloma are the same as those in multiple myeloma. These symptoms either do not go away during treatment or return after treatment^[4].

Bone pain is the most common symptom. The pain is usually felt in the lower back or ribs. If the bones continue to weaken from the cancer, they can even break^[4].

Other symptoms that may indicate your treatment is not working include:

• Weakness and tiredness
• Purple spots on your skin
• Frequent infections
• Shortness of breath
• Loss of appetite^[4]

If symptoms continue through treatment, it is a sign that the current treatment is not working. You should talk to your doctor if you continue to experience symptoms^[4].

How Is Refractory Multiple Myeloma Diagnosed?

Once you start treatment, your doctor will do regular blood tests and imaging scans to see if your cancer has responded^[8]. Tests that examine the blood, bone marrow, and urine are used to diagnose and monitor multiple myeloma and other plasma cell conditions^[4].

Blood tests are an important part of monitoring. You will get a complete blood count (CBC) at every checkup. This test measures the amount of red blood cells, white blood cells, and platelets in your blood. Multiple myeloma can lower the numbers of these cells^[8].

Blood chemistry tests check levels of proteins and other substances in your blood. Multiple myeloma can cause high calcium levels and low levels of the protein albumin. Other blood tests detect high or low levels of certain antibodies that multiple myeloma can affect^[8].

Urine tests check your urine for proteins and creatinine, a waste product your body makes when it breaks down protein. High levels of certain proteins can be a sign that multiple myeloma has damaged your kidneys. For these tests, you may need to collect all of your urine for 24 hours^[8].

Imaging tests let your doctor look inside your body to see whether your cancer has gotten smaller or if it has grown. Tests you might get include:

• An X-ray, which uses radiation in low doses to make images of your bones and can show areas of bone loss from multiple myeloma
• An MRI (magnetic resonance imaging), which uses powerful magnets and radio waves to make three-dimensional pictures of your bones
• A CT scan (computed tomography), which is a powerful X-ray that makes three-dimensional images of your bones to find any areas of cancer
• A PET scan (positron emission tomography), which uses a radioactive sugar that cancer cells absorb, then a special camera takes pictures to show areas of cancer in your body^[8]

Bone marrow tests involve your doctor removing a sample of liquid or tissue from your bone marrow. A laboratory then checks the sample under a microscope to look for cancer cells^[8].

Special tests may be done on biopsy samples to monitor how treatment is going, determine the subtype of refractory multiple myeloma, and identify the proper treatment options. These include:

• Cytogenetic analysis: The chromosomes in cancer cells are counted and checked for any changes or damage
• FISH test (Fluorescence in situ hybridization): A laboratory test to identify and count the genes or chromosomes in cancer cells. DNA containing fluorescent dye binds to specific genes and chromosomes and lights up when viewed under a microscope
• Flow cytometry: A laboratory test that measures the number of cells, the percentage of live cells present, and characteristics such as the size, shape, and markers on the cell surface of a bone marrow tissue sample^[4]

Treatment Options for Refractory Multiple Myeloma

Because refractory multiple myeloma patients have already received one treatment that has not been effective, doctors need to decide which treatment option should be used next^[4].

Treatment options depend on several factors, including your overall health, symptoms, treatments you may have tried already, and the risk of the cancer coming back. Stem cell transplants are common for multiple myeloma, but they are less commonly used for refractory or relapsed disease^[4].

Treatment of relapsed or refractory multiple myeloma includes:

• Watchful waiting or active surveillance for patients whose disease is stable and who have no symptoms present^[4]
• For patients who were in remission for at least one year, the same drug may be used again^[4]
• Targeted therapy with monoclonal antibodies such as daratumumab or elotuzumab^[4]
• Targeted therapy with proteasome inhibitors such as bortezomib^[4]

Most people with multiple myeloma will have several cycles of remissions and relapse during the treatment course. This requires multiple treatment adjustments over time^[1]. Recent advances in treatment have improved survival outcomes in patients, with novel therapies and combination approaches resulting in better outcomes^[1].

Your healthcare team will work with you to develop a comprehensive care plan. It is important to keep open communication with your doctor about how you are feeling and any symptoms you experience during treatment.