More than 20,000 new cases of multiple myeloma are diagnosed in the United States each year. Myeloma usually occurs in middle aged and older individuals. Statistics show that the mean age of individuals diagnosed with multiple myeloma is 62 years for men and 61 years for women. Dramatic advances in treatment for multiple myeloma in the past several years have given many patients an improved outlook.
If you have been diagnosed with multiple myeloma, you probably have many questions about the disease, how it is likely to be treated, and what happens when treatment is completed. This treatment summary, which is based on the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™), will help you understand the best available treatments for multiple myeloma. Talk to your doctors about these therapies so that together you can decide on a cancer treatment plan that is right for you.
Background
Myeloma is a cancer of the immune system in which abnormal plasma cells are found in the bone marrow. Plasma cells are a type of white blood cells that normally produce antibodies to help fight infections. In myeloma, large numbers of abnormal plasma cells (myeloma cells) are produced, causing disruptions of normal bone marrow function, destruction of the surrounding bone, and production of excessive amounts of monoclonal protein called M-protein. Myeloma affects sites in the body where bone marrow is normally active, such as within the bones of the spine and the skull, pelvis, rib cage, and areas around the shoulders and hips
Multiple myeloma starts as a single cell that has undergone a genetic change. It then divides again and again until there is a group of cells, all with the same genetic defect. These cells produce proteins in greater quantities than normal cells, making the blood thicker and causing a variety of problems. Monitoring the quantities of these proteins is one way to monitor the progress of the disease.
Plasmacytomas are plasma cell tumors that are located either in the bone (osseus plasmacytoma) or outside the bone (extraosseous plasmacytoma). Plasmacytoma that is localized to a single site is called solitary plasmacytoma; multiple plasmacytomas that occur throughout the body are called multiple myeloma. Multiple myeloma can be either smoldering, which means causing no symptoms, or active, meaning that it causes symptoms.
Multiple myeloma is much more common in older patients, with an average age at diagnosis of 62 years. More than 75% of patients with multiple myeloma are older than 70 years, and it rarely occurs in patients younger than 35 years. African Americans and men are more likely to develop multiple myeloma than Asians or women. People who have had a close family member with the disease are more likely to get it than those with no family history.
Multiple myeloma is part of a spectrum of abnormalities in the plasma cells that range from benign (meaning noncancerous) disorders, such as monoclonal gammopathy of unknown significance (MGUS), which is a risk factor for multiple myeloma, to asymptomatic or smoldering myeloma, to active multiple myeloma. In fact, multiple myeloma usually occurs in people who have been previously diagnosed with MGUS, although many people with MGUS never develop cancer.
Diagnosis
People with multiple myeloma may have symptoms that lead them to contact their doctors. Pain in the bones, especially in the back and ribs, and broken bones are common. Some multiple myeloma patients report excessive thirst, frequent urination, unexplained weight loss, fatigue or weakness, or frequent infections. Some patients have nausea or vomiting. All of these symptoms can be related to other causes, but because they can also be serious, anyone who has any of these symptoms should discuss them with a doctor.
To diagnose multiple myeloma, the doctor will usually order a number of tests, including an examination of blood and urine samples; a skeletal survey (x-rays of all your bones); and a bone marrow biopsy. The doctor will order genetic tests on your bone marrow sample and blood to find out which chromosomal abnormality is present. Depending on your particular circumstances, the doctor may also recommend an MRI of your spine, a CT scan or PET/CT, a bone density test, and other blood tests. If you have only one area that has a possible tumor, the doctor may order a biopsy of that site.
Your doctor will diagnose whether you have multiple myeloma based on several things:
- Presence of 10% or more plasma cells in the bone marrow aspirate (biopsy sample)
- M-protein levels of 30 g/dL or higher in a urine or blood sample
- High calcium in the blood (which suggests bone loss), poor kidney function, anemia, or bone disease
The Pathology Report
The results of the biopsy will indicate whether abnormal plasma cells are present. Specialized genetic tests may reveal genetic and chromosomal abnormalities and help in determining the genetic subtype of myeloma. The specific type of the genetic change in the myeloma cells provides important information about how aggressive the cancer is likely to be. Currently, the type of treatment doctors recommend is not based on this risk of the cancer being more aggressive; however, there is some evidence suggesting that patients with higher-risk myeloma may benefit from more aggressive therapy or from treatment with novel (new) agents.
While any cancer diagnosis is a cause for concern, the outlook in multiple myeloma depends on several things: how widespread the disease is, how aggressive it is, and whether or not you have symptoms. Your general health other than the cancer is also important in predicting the probable course of the disease and selecting a treatment.
In general the more localized any cancer is, the better the chance that it can be cured. If the cancer has spread to different parts of your body, it probably can’t be cured; however, with appropriate treatment, the cancer may be controlled and you may live a high-quality life for years.
Multiple Myeloma Staging
A formal system called staging is used to identify how widespread and aggressive your cancer is. Two staging systems are used for multiple myeloma. One is based on the blood levels of two markers: beta-2-microglobulin and albumin. This staging system is called the International Staging System (ISS). The other, known as the Durie-Salmon staging system, looks at protein quantities, whether there is extra calcium in your blood (indicating bone loss), whether you are anemic, and whether your bones are normal or have evidence of disease.
Treatment for Multiple Myeloma
No single multiple myeloma treatment works for all patients, and recommendations on the best treatment vary from person to person. Your doctor will determine the best treatment plan for you based on the cancer stage and your symptoms, age, and general health.
Not everyone diagnosed with myeloma needs treatment immediately. If you have asymptomatic myeloma, you will undergo close observation (sometimes called watchful waiting) rather than active treatment.
If you have solitary plasmacytoma, local therapy may cure the disease. For more information about plasmacytoma and its treatment, see the NCCN Plasmacytoma Treatment Summary for People with Cancer
TM
, which will be available soon.
Disease that has spread beyond a solitary plasmacytoma is called multiple myeloma. Treatments for multiple myeloma can be very effective at halting or slowing disease progress by decreasing the number of abnormal plasma cells and controlling symptoms such as anemia, infections, and pain, thus improving quality of life. Several treatment options are available to control multiple myeloma, but none currently available can cure it.
If you are diagnosed with multiple myeloma, the treatment strategy depends on whether you have symptoms or not. Multiple myeloma remains stable for a long time. If you have early-stage disease and no symptoms, your recommended strategy is to visit the doctor at 3- to 6-month intervals to monitor whether your disease progresses, and to defer active treatment until it does (observation or watchful waiting). After symptoms develop, one or more of the following multiple myeloma treatments is recommended:
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Systemic chemotherapy (drugs administered, either alone or in combination, that travel throughout your body)
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Targeted therapy with agents such as thalidomide (Thalomid), lenalidomide (Revlimid), and bortezomib (Velcade)
- Steroid therapy
- Stem cell transplantation
Your doctor should provide you with a written care plan explaining what treatments you will have, when they will occur, how often (if you will have chemotherapy or therapy with biologic agents), and what side effects you may experience. You will be asked to sign an informed consent document indicating that you have been told about your treatment and what to expect.
It is very important that you ask your doctor or nurse every question you have. Cancer and its treatment are complicated, and most patients have questions.
For example, each of these treatments has side effects. Some side effects can be anticipated, and you can get treatment to reduce their severity. Talk with your doctor about what to expect from your treatment and how these side effects can be prevented, reduced, managed, or eliminated. Also talk to your doctor about any side effects that you may experience once treatment starts. Treating side effects does not alter how effective therapy is, but it can make you feel better.
Treatment for Smoldering Myeloma
Multiple myeloma that does not cause any symptoms, such as bone pain, anemia, impaired kidney function, or increased susceptibility to infections, is called smoldering myeloma. The recommended strategy for patients with smoldering myeloma is observation, or visiting the doctor at 3- to 6-month intervals to monitor whether the disease progresses.
Although your cancer probably cannot be cured, if it is not causing symptoms you can safely wait to start treatment until symptoms occur, and live a high quality life for years. In fact, clinical trials have shown no advantage to beginning treatment early. In addition, treatment always includes the risk of unwanted side effects, so you should begin therapy only when the benefits of treatment are expected to outweigh this risk.
If tests show evidence of bone disease or you are osteopenic (have a low bone mineral density), your doctor may recommend that you begin taking bisphosphonates to prevent bone loss. Because the value of beginning bisphosphonate treatment before any symptoms occur is not clear, NCCN recommends that this treatment be given in a clinical trial if possible. Clinical trials will allow doctors to find out whether starting this type of therapy early is helpful.
During follow-up visits with your doctor every 3 to 6 months, you will undergo a complete physical exam, discuss your health, and have blood tests. Once a year, or more often if you have symptoms, your doctor will also perform a bone survey. You will only need a bone marrow biopsy if symptoms occur or the findings from the blood tests show that one is needed. Some patients can stay on observation for months to years before needing active treatment. When the myeloma begins to progress, you doctor will recommend that you begin treatment as described below.
Treatment for Active (Symptomatic) Multiple Myeloma
Treatment for multiple myeloma typically begins only when the disease causes symptoms, such as anemia, bone pain, and kidney and other organ damage. In the past several years, new drugs for multiple myeloma have changed the outlook for people with this disease and more than doubled survival. These new treatments are both disease-directed, meaning that their purpose is to reduce the cancer, and symptom-directed, meaning that they are aimed at reducing the disease symptoms.
Treatment for multiple myeloma typically involves systemic chemotherapy, which consists of anticancer drugs that are administered either alone or in combination and travel throughout your body. The specific regimen (combination of drugs) that is right for you depends on several factors, including your general health and any treatments you may have had in the past. Another important consideration is the possible side effects of the drugs. Your doctor will ask questions about you and your lifestyle, the activities that are important to you, and your specific concerns, and will take these into consideration when recommending a treatment strategy for you.
Newly Diagnosed Active Multiple Myeloma
The first step in treatment is called induction therapy. Induction therapy is designed to get the myeloma cells under control. Clinical trials have shown that several different combinations of drugs are effective against multiple myeloma.
Because the choice of initial therapy may affect stem cell collection for transplant, before you begin systemic treatment, your doctor will decide whether stem cell transplantation (formerly called bone marrow transplantion) is an option for you. This decision will depend on your general health, such as how well some of your major organ systems function, and your personal choice.
Stem cell transplantation is a method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. These stem cells can be taken from you (autologous; collected early and stored for later use) or from another genetically similar donor (allogeneic; collected from a sibling, for example, although the donor can be unrelated). See section on Stem Cell Transplantation.
Patients who are not transplant candidates
If you are among the patients who cannot have a stem cell transplant or have decided that you do not want one, induction (first-step) therapy is continued until the maximum possible response is achieved. Initial treatment has changed substantially with FDA approval of new drugs like thalidomide (Thalomid), bortezomib (Velcade), and lenalidomide (Revlamid). Melphalan (Alkeran) and prednisone continue to be an option for elderly patients; however, newer and more effective combinations have emerged. These newer combinations, such as melphalan, prednisone, and thalidomide; or bortezomib, melphalan, and prednisone, are recommended for patients who are not eligible for transplantation. In addition, single-agent dexamethasone (Decadron, DexPak), dexamethasone in combination with thalidomide or liposomal doxorubicin (Adriamycin) and vincristine (Oncovin, Vincasar), or lower-dose dexamethasone in combination with lenalidomide may be offered to you depending on your individual clinical situation.
After the maximum possible response is achieved, you will then either enter follow-up, which includes stopping the drugs but undergoing periodic blood tests, bone surveys, and imaging if needed or your doctor may recommend maintenance therapy. Maintenance therapy involves continuing to take drugs long-term to keep the disease controlled. Options are thalidomide with or without prednisone; interferon; or steroids such as dexamethasone or prednisone. If possible, NCCN recommends participating in a clinical trial to test whether maintenance therapy provides better results than follow-up.
Several options are available if your myeloma does not respond to initial therapy or recurs (comes back). These are detailed in the later section on Treating Relapsed or Refractory Multiple Myeloma.
Patients who are transplant candidates
If you are considered a candidate for stem cell transplantation, your initial therapy will not include melphalan because this drug has a toxic effect on stem cells. Your doctor may instead recommend drugs in combinations of 2 or 3, or dexamethasone alone.
The drugs you may be given include bortezomib, dexamethasone, doxorubicin, lenalidomide, thalidomide, and vincristine. Your stem cells will probably be collected after starting induction treatment with these agents.
Once you show a response to induction therapy, your doctor may recommend a stem cell transplant or may consider delaying the transplant until after a relapse, if one occurs. NCCN strongly recommends autologous stem cell transplant as part of the frontline therapy for patients newly diagnosed with symptomatic myeloma rather than saving it as an option for after relapse.
Age, other health concerns besides your myeloma, and personal preference are also important factors that will help your doctor make the appropriate treatment recommendations.
If transplantation is not performed immediately after response to induction therapy, then additional therapy—often called maintenance therapy—is typically required to keep the myeloma under control. The role of maintenance therapy after induction therapy and before stem cell transplant is not very clear. Therefore, participation in a clinical trial is highly encouraged if one is available.
If you and your doctor decide that transplantation might be an option for you at some point in your treatment, your doctor will harvest enough of your own stem cells after induction therapy to allow two transplants later.
Stem Cell Transplantation
Transplants are rigorous treatments. High-dose systemic chemotherapy, also called conditioning therapy, is given to kill the myeloma cells. The dose is so high that the drugs also kill normal rapidly dividing cells in your body, like the blood cells responsible for your immune system responses. These blood cells are replaced with an infusion of blood and marrow, much like a blood transfusion. These cells then seed your own bone marrow and restore your blood and immune systems in a process call engraftment.
Engraftment usually occurs between 2 and 4 weeks after transplantation, and full recovery of your immune function can take up to several months. Your doctor will give you instructions about how to avoid infections because you are at increased risk until your immune system is functioning normally again. Your doctor will monitor the progress of the engraftment with frequent blood tests.
There are several types of stem cell transplantation. The first type— stem cell transplantation using your own stem cells—is called autologous stem cell transplant. With this procedure, you would first receive high-dose therapy to wipe out your bone marrow, and then have your own stem cells injected into your bloodstream to grow in your bone marrow, making new blood and immune cells. Although the high-dose therapy does have associated risks, you are not at risk for having your body reject the stem cells, because any remaining cells in your immune system recognize them as your own.
The second type of stem cell transplant, called allogeneic stem cell transplant, uses stem cells from a donor who is a close genetic match to you, most frequently a close relative. Because this is a high-risk procedure, allogeneic stem cell transplant is not used very often in myeloma and NCCN recommends patients undergo this type of transplant only in a clinical trial.
The initial conditioning regimen used for allogeneic transplantation is the same as that used for autologous transplantation. The potential advantages of allogeneic (from someone else) over autologous (from yourself) transplantation include that the new stem cells are myeloma-free and the possibility of inducing graft-versus-myeloma effect, which means that the donor bone marrow completely takes over and the myeloma cells are wiped out.
Graft-versus-myeloma effect can be enhanced by using donor lymphocyte infusions. NCCN recommends donor lymphocyte infusions for patients whose disease relapses after allogeneic transplantation. Lymphocytes are white blood cells, which are an important part of your immune system and help you fight infections.
The disadvantages of allogeneic stem cell transplants include the risk for graft-versus-host disease, in which the donor cells recognize the recipient’s tissue as “foreign” and the newly transplanted bone marrow attacks the recipient’s cells as if they were an infection. Even in centers with a great deal of experience, the risk associated with allogeneic stem cell transplantation for myeloma is quite high.
Another option is the “mini” allogeneic transplantation. In this procedure, the initial conditioning regimen is less toxic; therefore, this is better tolerated than full allogeneic transplantation. However, the benefit of mini allogenic transplant alone after initial induction therapy is unknown, and is currently not recommended. Mini allogeneic transplant may be an option after an autologous transplant; again, however, because information on the results of this treatment is limited, NCCN again recommends having this treatment only in a clinical trial.
More information on clinical trials is available in the Guide to Clinical Trials and Demystifying Common Clinical Trial Myths.
If your disease is stable after the transplant, you will either be observed, as described later,[link] or start maintenance therapy with thalidomide with or without prednisone; interferon alone; or steroids such as dexamethasone or prednisone.
If your own stem cells were used for your stem cell transplant, you may undergo a second transplant. Your doctor will determine whether a second autologous transplant is appropriate. A second transplant (also called tandem transplant), which is usually done within about 6 months of the first autologous transplant, is of limited benefit to patients who have a complete response (disappearance of all signs of disease) or near-complete response after the initial transplant. Only patients who have a partial response (decrease in the extent of disease) or stable disease (disease that is neither decreasing or increasing in extent or severity) after the first autologous transplant derive benefit from a second one.
If you have a response to the initial transplant, you will be followed up with blood tests at least every 3 months; bone surveys annually or if you have symptoms; and bone marrow biopsy if your doctor determines it necessary. You may also undergo imaging, as needed. If you experience a relapse, you will be treated as described in the next section.
Relapsed or Refractory Multiple Myeloma
If the myeloma returns (first relapse occurs) after the disease was stable for at least 6 months, the first strategy recommended by the NCCN myeloma panel is to administer the same treatment that stabilized the disease in the first place. In other words, induction therapy is repeated.
If the myeloma returns within 6 months of therapy, or you have refractory myeloma (which means that it is not controlled with the induction therapy), alternate therapy is needed.
Treatments involving bortezomib either alone or in combination with other drugs, or lenalidomide in combination with dexamethasone, are usually strongly preferred because their value in treating relapsed myeloma has been proven in large randomized trials. However, it is important to keep in mind that a variety of single and combination chemotherapy options are available for managing relapsing and refractory disease in addition to those containing bortezomib or lenalidomide. You and your physician can refer to the NCCN Guidelines™ for the treatment of multiple myeloma for a complete listing of available options. (Free registration is required to view the guidelines.)
Supportive Care
Supportive care, which is treatment to control the symptoms of multiple myeloma and reduce the side-effects of treatment, is crucial in the management of multiple myeloma. Supportive care continues throughout your therapy and beyond to help you live a higher-quality life and prevent undue risk to your vital organs from myeloma or its treatment.
If you experience pain, nausea or vomiting, fatigue, or other troublesome symptoms, let your doctor know. There is no reason to suffer when treatments are available that can help you feel better.
One treatment you may receive involves drugs called bisphosphonates, which control ongoing bone destruction and improve the chances of bone healing and recovery of bone mineral density. If you are treated with bisphosphonates, your doctor will monitor you for known side effects of these drugs, including kidney problems and a rare problem with the jawbone. If possible, any dental work you need should be done before you start taking bisphosphonates.
If you experience severe pain from disease in your bones, your doctor may recommend surgery, radiation, or both to reduce pressure on a nerve, spinal cord, or other crucial organ. If you have serious bone disease, your doctor may also recommend that you talk with an orthopedic surgeon about stabilizing bones in your legs or back to prevent fractures or treat those that already exist. Again, you should talk to your cancer care team about any pain you are having; with available drugs and new strategies, pain can be effectively reduced.
You may also need treatment to control the amount of calcium in your blood, to control anemia, or to remove some of the extra protein made by the myeloma cells. Your doctor will discuss these treatments with you if necessary.
Because multiple myeloma affects the number of infection-fighting white blood cells you have, you may be more susceptible to infections. Your doctor may recommend that you get vaccinated for pneumonia and influenza. If you develop a fever of 101°F or higher or any other symptoms of an infection, you should contact your physician promptly so he or she can decide if you need antibiotics. Your doctor may also recommend that you take preventative medications for other types of infections if you are taking drugs like dexamethasone or bortezomib.
Kidney problems are common in people with multiple myeloma, so it is important for you to drink enough fluids (2–3 liters per day) and avoid nonsteroidal anti-inflammatory drugs (NSAIDs), such as naproxen (Aleve, Naprosyn) or ibuprofen (Advil, Motrin). You should also undergo periodic monitoring of your kidney function if you are taking bisphosphonates over a long period of time.
Some chemotherapy drugs, such as doxorubicin, can affect the heart, and therefore you may need periodic testing to monitor your heart function. Make sure you discuss this possibility with your cancer care team and understand fully what you can expect if you are placed on a regimen that includes a drug like this.
Finally, blood clots may occur in people taking thalidomide or lenalidomide with dexamethasone. Your doctor may recommend that you take blood-thinning drugs before and during treatment.
These supportive care treatments are designed to ensure that you can enjoy the best possible quality of life.
Prognosis for Multiple Myeloma
In determining a prognosis (the likely course or outcome of a disease and its treatment) a doctor may look at multiple myeloma survival statistics taken from studies of large groups of patients. The average survival time has doubled in the past 5 years for people with multiple myeloma, and it has become a chronic disease for many patients. However, such statistics:
- Are estimates only
- Can vary widely with each cancer stage
- Are sometimes based on older data that do not reflect recent advances in early detection and treatment
- Cannot be used to precisely predict your survival
Your individual prognosis will be affected by many factors, including:
- Your age
- Your overall health
- The type, stage, grade, and other characteristics of your cancer
- Your response to the treatment(s) used
Clinical Trials
Clinical trials for new drugs hold great promise of further improving the prognosis for people with myeloma. You may want to find out whether you are eligible to participate in a clinical trial, in which new and experimental therapies are compared with standard treatments. More information on clinical trials is available in the Guide to Clinical Trials and Demystifying Common Clinical Trial Myths.