Multiple myeloma is a cancer that affects a type of white blood cell called a plasma cell. Plasma cells produce antibodies to help fight infection and disease. In multiple myeloma, cancerous plasma cells (myeloma cells) are found in the bone marrow, the spongy tissue inside bones that manufactures blood cells. When myeloma cells accumulate in the bones, they can crowd out normal cells and invade bone tissue, damaging and weakening bones.

Risk Factors

Scientists have found few risk factors for multiple myeloma. The risk of this cancer increases with age, with most people diagnosed with this cancer at age 65 or older. Multiple myeloma is almost twice as common among African-Americans as Caucasians, and slightly more prevalent in men than women. In some cases, patients have family members with myeloma. Some studies have suggested that workers in certain petroleum-related industries may be at a higher risk. A study by the American Cancer Society has found that being overweight or obese increases a person’s risk of developing myeloma. Many people with other plasma cell diseases like MGUS or solitary plasmacytoma will eventually develop multiple myeloma. 

Symptoms

Common symptoms of multiple myeloma include bone pain in the back and ribs; broken bones, usually in the spine; feeling weak or tired; excessive thirst; frequent infections and fevers; weight loss; nausea or constipation; and frequent urination.

Diagnostic Tests

Multiple myeloma is usually diagnosed by a blood test to identify high levels of a type of protein or antibody produced by myeloma cells. The doctor also may do a bone marrow aspiration or a bone marrow biopsy, two tests that involve taking a sample of cells or tissue from the bone marrow to examine for abnormalities under a microscope. Patients referred to the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins for multiple myeloma are seen by a team of doctors who specialize in this disease. Hematologists, oncologists and pathologists first carefully examine the myeloma cells to define the specific type of myeloma. A multidisciplinary team of doctors then determines the optimal treatment plan for the patient.

Other tests for multiple myeloma include a urine test to check for a type of protein called Bence Jones, which can clog the kidneys and damage them; or X-rays to check for broken or thinning bones. Other imaging tests, like a computed tomography (CT) scan or magnetic resonance imaging (MRI) may be recommended. The CT scan is an X-ray machine linked to a computer that takes a series of detailed pictures of your bones. MRI is a powerful magnet linked to a computer that is used to make detailed pictures of the bones.

Staging

Staging is a process used to determine how far the cancer has spread. It’s important for doctors to know the stage of disease so they can plan the best treatment. Doctors may describe multiple myeloma as smoldering, Stage I, Stage II or Stage III. 

The stage depends on blood levels of calcium, hemoglobin and monoclonal immunoglobulin, and takes into account whether the cancer is causing problems with your bones or kidneys. High blood calcium levels are related to advanced bone damage; bones contain high levels of calcium, so bone destruction releases calcium into the blood. Hemoglobin is a substance in red blood cells that carries oxygen; low levels indicate that myeloma cells occupy much of the bone marrow and that not enough space is left for the normal marrow cells that produce red blood cells. Large amounts of monoclonal immunoglobulin indicate that many malignant plasma cells are present and are producing that abnormal protein.

• Smoldering multiple myeloma is early disease without any symptoms. For example, there is no bone damage.
• Stage I means a relatively small number of myeloma cells are found. Hemoglobin levels are only slightly below normal and bone X-rays may appear normal or show only one area of damage.
• Stage II means a moderate number of myeloma cells are present and other features are between stage I and stage III.
• Stage III means a large number of myeloma cells are found. In addition, patients have at least one of the following: a low hemoglobin level, a high blood calcium level, three or more areas of bone damage from cancer, and a large amount of monoclonal immunoglobulin in blood or urine. 

Another staging system classifies multiple myeloma into three stages based on blood levels of beta-2 microglobulin (a protein on the surface of cells that is released into the bloodstream when cells die) and albumin (a protein that regulates the volume and pressure of plasma).

Current Treatments

Patients who have multiple myeloma but do not have symptoms of the disease may not require immediate therapy, but they do need careful follow-up. Patients who need treatment usually receive chemotherapy and sometimes radiation therapy. In some cases, patients also may receive biological therapy -- the use of substances to boost the immune system to fight cancer. Our physicians continue to search for new chemotherapeutic drugs that might be effective in treating this resistant form of cancer.

Physicians at the Johns Hopkins Kimmel Cancer Center take an aggressive, comprehensive approach to multiple myeloma treatment, from state-of-the-art testing to involving patients in ongoing clinical trials to the use of established therapies and bone marrow transplantation. Since myeloma can affect the bones, our doctors interact with orthopedic experts as necessary to bring you the best care. Our priority is to achieve a long-term remission of the disease. One treatment option offered early in the course of the disease is bone marrow transplantation -- a procedure in which diseased bone marrow is removed and, after high-dose chemotherapy, replaced with healthy marrow. Cancer center doctors pioneered the technique of bone marrow transplantation and remain leaders in improving the effectiveness and safety of this procedure.

Our physicians have been successful in extending the option of allogeneic transplants -- a curative treatment for multiple myeloma -- to patients up to the age of 65. Allogeneic bone marrow transplants are transplants using donor marrow. For myeloma patients who are not candidates for allogeneic transplants, another treatment option at the Kimmel Cancer Center is stem cell transplantation, which can be performed on patients up to age 70. Stem cell transplantation involves stimulating the bone marrow with growth factors that cause the stem cells (the cells in the marrow from which blood cells arise) to enter the bloodstream. These cells then are collected in the same way a patient would donate platelets. The cells are later re-infused into the patient after high-dose chemotherapy to re-populate the bone marrow. Because more stem cells can be collected in this fashion than in a traditional bone marrow transplantation, the hospital stay can be shortened. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, along with other major medical centers around the country, is cooperating in large group studies to refine the technique and compare it to traditional marrow transplantation.

Our doctors have pioneered an immune approach used in conjunction with autologous transplantation (when bone marrow is removed from a patient and reinfused after high-dose drug treatment) to destroy remaining cancer cells and increase the possibility of cure for myeloma and leukemia patients. They also have developed a technique called graft engineering, which involves a series of steps to remove certain harmful cells and add other useful cells to the bone marrow before it is infused into a patient.

Multiple MyelomaTreatments

Chemotherapy – Myeloma treatment generally involves anticancer drugs, which enter the bloodstream to affect myeloma cells throughout the body. There are many drugs available to treat myeloma. Your physician will recommend one or more medications that are appropriate for you. The medications can be administered as pills or as slow infusions into your veins. Chemotherapy is typically administered every two to three weeks for a number of cycles. Side effects can depend on which drugs were given and how much, but include fatigue, hair loss, poor appetite, nausea or vomiting, diarrhea, or infertility. 

Some myeloma patients receive biological therapy – treatments that improve the body’s defenses against the disease. The drug Velcade (bortezomib) is relatively new for myeloma; it interferes with the signals cells use to control their growth, stopping the breakdown of proteins within cells. This leads to a build up of protein, which causes the cell to die. The drug is injected into a vein. Like chemotherapy, it is offered in cycles of treatment, with breaks in between. Patients are treated twice a week for two weeks and then have a week's break. Side effects include tiredness, sickness, diarrhea or constipation, loss of appetite, pins and needles or numbness in fingers and toes, and increased risk of bruising or bleeding.

Interferon is a biological therapy sometimes given as a maintenance therapy for myeloma. It works by stopping cancer cells from growing and multiplying. It also stimulates the immune system by encouraging healthy disease-fighting cells to attack cancer cells. It also encourages cancer cells to send out chemicals that attract the immune system cells to them. The drug is injected under the skin two or three times a week. Side effects include flu-like symptoms after injection. 

Some medical centers including Johns Hopkins are testing new medications in clinical trials. One such targeted therapy is oncolytic virotherapy, in which viruses specifically infect and kill the malignant plasma cells, leaving normal cells intact.

Other medications – Myeloma cells can cause bone to weaken and dissolve. Drugs called bisphosphonates can help the bones stay strong by slowing down this process. Two such medications are pamidronate (Aredia) and zoledronic acid (Zometa). These drugs are infected into a vein. Most patients are treated once a month at first, but may be able to be treated less often later on, if they are doing well. There is a rare but serious side effect called osteonecrosis of the jaw, in which part of the jaw bone dies. Maintaining good oral hygiene can help.

Radiation therapy – Radiation therapy uses high-energy rays to kill myeloma cells by damaging the genetic material they contain. For people with just one area of myeloma, the radiation can be targeted to the bone or part of the body where myeloma cells have collected. People receive radiation for 4 to 5 weeks. It also can be used to treat areas of bone damaged by myeloma that have not responded to chemotherapy and are causing pain. 

Some patients with more advanced disease may receive radiation to their whole body before stem cell transplantation. Radiation treatments may be given two to three times a day for several days. 

The side effects of radiation therapy, including fatigue, can depend on the dose of radiation and the part of the body that is treated. Skin in the area being treated may become red, dry, and tender.

Plasmapheresis -- In this treatment, patients are hooked up to a machine that removes blood from a vein, separates blood cells from the plasma, and then returns it to the patient. The discarded plasma contains the abnormal antibody protein produced by the myeloma cells. It can be replaced with a salt solution and plasma from donors. The treatment can be helpful in some cases if myeloma proteins build up, thicken the blood, and interfere with circulation. Although plasmapheresis can relieve some symptoms, it does not kill myeloma cells. 

Bone marrow transplant / Stem cell transplant – A bone marrow transplant gives a patient healthy stem cells – immature cells that grow into different parts of the blood – taken from the marrow, the soft, fatty tissue inside the bones, replacing bone marrow that is either not working properly or has been destroyed by chemotherapy or radiation. Stem cells may be taken from the patient before getting chemotherapy or radiation. They also may come from a relative or other donor, or from umbilical cord blood.

Most patients get high doses of chemotherapy, radiation, or both, before the bone marrow transplant to kill any cancer cells that might remain and make room for new stem cells to grow. Doctors then deliver the stem cells through a tube injected into the bloodstream. They find their way into the bone marrow and begin reproducing to make healthy new blood cells. While receiving stem cells, patients may experience pain, chills, fever, hives, chest pain or other symptoms.

Vaccine – Researchers at Johns Hopkins Kimmel Cancer Center and other medical centers across the country are researching and testing novel vaccines to help fight myelomas.

Research/Clinical Trials

Immunotherapy

Researchers led by Ivan Borrello, M.D., have developed a novel personalized cancer treatment approach called adoptive T cell therapy using patients’ own immune cells to fight their cancer. This approach uses cells from the bone marrow known as marrow infiltrating lymphocytes, or MILs. Scientists retrieve a patient’s MILs from the bone marrow, expand their numbers and coat the cells with immune-activating antibodies in a cell therapy lab at Johns Hopkins, then infuse them back into the patient’s bloodstream where they seek out and destroy cancer cells. The treatment is being tested in clinical trials. 

Read more about immunotherapy in our magazine, Promise & Progress

Multiple myeloma experts at the Johns Hopkins Kimmel Cancer Center have two main research interests in developing new therapies:

(1) Medications that target multiple myeloma stem cells: Dr. William Matsui’s research laboratory in 2004 was the first to identify multiple myeloma stem cells, and then demonstrate that these cells were relatively resistant to most agents used to treat patients with the disease. Through clinical trials led by Dr. Carol Ann Huff, clinicians are testing new agents that target cancerous stem cells through signaling pathways that affect stem cell development.

(2) Immunologic approaches: Dr. Ivan Borrello has developed a vaccine that secretes granulocyte-macrophage colony-stimulating factor (GM-CSF), a protein that helps the body fight infection. Through various clinical trials, Dr. Borrello and colleagues are testing the vaccine in combination with biological therapies, chemotherapy or stem cell transplants to build a stronger immune system and kill more cancer cells.