Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.
Eyes front and ears open. Class is now in session.
The rare disease that we will be learning about today is:
Multiple Myeloma
Also known as plasma cell myeloma or simply myeloma.
What is Multiple Myeloma?
- Multiple myeloma is that affects plasma cells. These are white blood cells that produce antibodies.
- In its early stages, often no symptoms are present.
- Multiple myeloma is a relatively uncommon cancer. In the United States, the lifetime risk of getting multiple myeloma is 1 in 143 (0.7%).
- The American Cancer Society’s estimates for multiple myeloma in the United States for 2017 are:
- About 30,280 new cases will be diagnosed (17,490 in males and 12,790 in females).
- About 12,590 deaths are expected to occur (6,660 in males and 5,930 in females).
- MM accounts for 10% of all hematologic cancers. The age-adjusted annual incidence of MM is 4.3 cases per 100,000 white men, 3 cases per 100,000 white females, 9.6 cases per 100,000 black males, and 6.7 cases per 100,000 black females.
- The median age of patients with MM is 68 years for males and 70 years for females. Only 18% of patients are younger than 50 years, and 3% of patients are younger than 40 years.
- The male-to-female ratio of MM is approximately 3:2.
- When B cells respond to an infection, they mature and change into plasma cells. Plasma cells make the antibodies (also called immunoglobulins) that help the body attack and kill germs. Lymphocytes are in many areas of the body, such as lymph nodes, the bone marrow, the intestines, and the bloodstream.
- Plasma cells, however, are mainly found in the bone marrow. Bone marrow is the soft tissue inside some hollow bones. In addition to plasma cells, normal bone marrow has cells that make the different normal blood cells.
- When plasma cells become cancerous and grow out of control, they can produce a tumor called a plasmacytoma. These tumors generally develop in a bone, but they are also rarely found in other tissues.
- If someone has only a single plasma cell tumor, the disease is called an isolated (or solitary) plasmacytoma. If someone has more than one plasmacytoma, they have multiple myeloma.
- Relapsed multiple myeloma
- Relapsed multiple myeloma, also known as recurrent myeloma, is when the cancer returns after treatment or a period of remission.
- Since multiple myeloma does not have a cure, it is likely that at some point patients will relapse.
- When faced with relapsed myeloma, it will be important to discuss your treatment with your doctor. Patients with relapsed myeloma should also seek a second opinion from a doctor with expertise in treating myeloma.
- In fact, most doctors will encourage patients to see more than one doctor before proceeding with treatment.
- With all of the new myeloma drugs being developed, there are number of treatment options for relapsed myeloma.
- Refractory multiple myeloma
- Refractory myeloma is when myeloma is not responsive to therapy. Refractory myeloma may occur in patients who never see a response from their treatment therapies or it may occur in patients who do initially respond to treatment, but do not respond to treatment after relapse.
- It is often recommended that refractory myeloma patients seek a second opinion before beginning a new treatment regimen. Doctors at larger cancer centers in particular may have more knowledge about treating multiple myeloma and access to more clinical trials specifically for patients with relapsed or refractory disease.
- Fortunately, there are many treatment options for patients with refractory myeloma. Refractory myeloma patients often have a different drug added to their treatment regimen, or a different combination of drugs may be used as a second-line therapy.
How Do You Get It?
- The cause of multiple myeloma has not yet been identified. Although scientists have made advancements in understanding how multiple myeloma develops, it is unclear as to what exactly causes the disease.
- Recent studies have found that abnormalities of some oncogenes (such as MYC) develop early in the course of plasma cell tumors. Changes in other oncogenes (such as the RAS genes) are more often found in myeloma cells in the bone marrow after treatment, and changes in tumor suppressor genes (such as the gene for p53) are associated with spread to other organs.
- Researchers have found that patients with plasma cell tumors have important abnormalities in other bone marrow cells and that these abnormalities may also cause excess plasma cell growth. Certain cells in the bone marrow called dendritic cells release a hormone called interleukin-6 (IL-6), which stimulates normal plasma cells to grow. Excessive production of IL-6 by these cells appears to be an important factor in development of plasma cell tumors.
- The risk factors for multiple myeloma are not conclusive, because the cause of multiple myeloma is not known. Researchers believe that multiple myeloma is most likely the result of many risk factors acting together
- Sex
- Males are slightly more likely to develop multiple myeloma than females.
- Age
- The most significant risk factor for multiple myeloma is age, as 96% of cases are diagnosed in people older than 45 years, and more than 63% are diagnosed in people older than 65 years. Thus, it is thought that susceptibility to multiple myeloma may increase with the aging process.
- Genetic/Hereditary Factors
- Multiple myeloma seems to run in some families. Someone who has a sibling or parent with myeloma is 4 times more likely to get it than would be expected. Still, most patients have no affected relatives, so this accounts for only a small number of cases.
- Race and Ethnicity Factors
- Multiple myeloma is more than twice as common in African Americans than in white Americans. The reason is not known.
- Myeloma is rare among people of Asian descent, with an incidence of only 1-2 cases per 100,000 population. According to a study of the ethnic disparities among patients with MM, Hispanics had the youngest median age at diagnosis (65 years) and whites had the oldest (71 years). Asians had the best overall survival rates, while Hispanics had the worst.
- Environmental Factors
- People who were exposed to radiation from an atomic bomb blast had a higher risk of multiple myeloma. Exposure to lower levels of radiation may also increase the risk of multiple myeloma. At most, this accounts for a very small number of cases.
- 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 monoclonal gammopathy of undetermined significance (MGUS) or solitary plasmacytoma will eventually develop multiple myeloma.
- Sex
What Are The Symptoms?
- The most common multiple myeloma symptoms may include:
- Bone pain or bone fractures
- Fatigue
- Increased vulnerability to infections
- Increased or decreased urination
- Restlessness – eventually followed by extreme weakness and fatigue
- Confusion
- Increased thirst
- Nausea and vomiting
- Loss of appetite and weight loss
- Impaired kidney function
- Impaired kidney function can result in a number of additional complications and is an effect of the kidneys being overworked by the excess protein and calcium in the blood. Indications of impaired kidney function may appear on blood tests or urine tests.
- Constipation
- Mental fogginess or confusion
- Weakness or numbness in your legs
- Bone lesions
- Bone pain or fractures are caused by tiny fractures in the bone (lytic bone lesions) made by the accumulation of plasma cells; weakened bone structure.
- Low blood count
- Low levels of red blood cells in the blood cause anemia related fatigue. Low blood count may also include low levels of white blood cells which increase susceptibility to infections and weaken the immune system.
- Hypercalcemia
- Changes in urination, restlessness, confusion, increased thirst, nausea and loss of appetite are usually a result of high levels of calcium in the blood.
How Is It Treated?
- Multiple Myeloma has a survival ranging from 1 year to more than 10 years. Median survival in unselected patients with MM is 3 years. The 5-year relative survival rate is 46.6%. Survival is higher in younger people and lower in the elderly.
- Conventional therapy: Overall survival is approximately 3 years, and event-free survival is less than 2 years.
- High-dose chemotherapy with stem-cell transplantation: The overall survival rate is greater than 50% at 5 years.
- Infections are an important cause of early death in Multiple Myeloma
- In a United Kingdom study, 10% of patients died within 60 days after diagnosis of MM, and 45% of those deaths were due to infection.
- In a Swedish study, 22% of patients died of infection within the first year after diagnosis.
- The risk of both bacterial infections (eg, meningitis, septicemia, pneumonia) and viral infections (eg, herpes zoster, influenza) was seven times higher in patients with MM than in matched controls.
- The Swedish investigators also found that the risk of infections has increased in recent decades, and they argue that the use of more intensive treatment measures for Multiple Myeloma (ie, newer drugs and high-dose chemotherapy with transplantation) has contributed to the increased risk.
- There are two types of therapy for Multiple Myeloma: One type of therapy is to control the myeloma or kill myeloma cells. The other is to alleviate symptoms and manage complications of the disease (such as bone damage) as well as side effects of treatment.
- Treatment includes medications, stem cell transplants, radiation, surgery, bisphosphonates
- There is no cure for Multiple Myeloma.
- Medications for multiple myeloma
- Monoclonal Antibodies
- Darzalex™ (daratumumab): is the first monoclonal antibody approved for use in multiple myeloma
- Empliciti™ (elotuzumab): is a monoclonal antibody approved for use in multiple myeloma. Empliciti is made by Bristol-Myers Squibb and AbbVie.
- Blenrep (belantamab mafodontin): Approved for relapsed and refractory disease in August 2020 (in US and EU).
- Sarclisa (isatuximab)
- Immunomodulatory Drugs
- Revlimid® (lenalidomide): Oral medication that is effective across the spectrum of myeloma disease.
- Pomalyst® (pomalidomide): Newer IMiD that is similar to Revlimid but is more potent. It is FDA approved for use in patients with relapsed/refractory myeloma and is being studied in other types of patients.
- Thalomid® (thalidomide): Older drug shown to be effective across the spectrum of myeloma disease; peripheral neuropathy (nerve problems) is a common side effect and can be irreversible. It is infrequently used in the US.
- Proteasome Inhibitors
- Ninlaro (ixazomib): The U.S. Food and Drug Administration granted approval for Ninlaro (ixazomib). Ninlaro is the first oral proteasome inhibitor and is approved in combination with Revlimid (lenalidomide) and dexamethasone.
- Velcade® (bortezomib): Medication used across the entire spectrum of myeloma disease. Given as an injection under the skin (subcutaneously) or intravenously. Patients who have the DNA alteration t(4;14) should receive a treatment regimen that includes a proteasome inhibitor.
- Kyprolis® (carfilzomib): Newer proteasome inhibitor given intravenously. It is FDA approved for use in
patients with relapsed/refractory myeloma and is being studied in other types of patients.
- Chemotherapy
- Doxil® (doxorubicin HCl liposome injection): Drug given intravenously in patients with relapsed/refractory myeloma, usually in combination with Velcade. Side effects include mouth sores, swelling, blisters on the hands or feet, and possible heart problems. It is less frequently used.
- Alkylator chemotherapy: Other types of chemotherapy drugs that have been used for many years to treat myeloma. They may be used in combination with other types of myeloma drugs. Examples are melphalan and cyclophosphamide.
- Histone deacetylase inhibitor
- Farydak® (panobinostat): Farydak® is a histone deacetylase inhibitor that is administered in combination with Velcade® (bortezomib) and dexamethasone for patients with relapsed/refractory multiple myeloma. It is administered as an oral medication.
- Steroids (corticosteroids)
- Dexamethasone (dex) and prednisone: Drugs used for decades to treat myeloma throughout the spectrum of disease; used in combination with other myeloma drugs.
- Nuclear export inhibitor
- Xpovio (selinexor): First approved as a combination treatment in 2019.
- Monoclonal Antibodies
- Stem cell transplants
- A stem cell transplant, in combination with high dose chemotherapy, is a treatment that offers a chance for durable remission of multiple myeloma. High-dose chemotherapy, though effective in killing myeloma cells, also destroys normal blood-forming cells, called hematopoeitic stem cells, in the bone marrow. Stem cell transplantation replaces these important cells.
- Bone marrow transplants are no longer done in multiple myeloma. Stem cells are collected after approximately four cycles of initial (induction) myeloma therapy in order to reduce the amount of myeloma cells. Medications that stimulate the production of stem cells (called mobilizing) are often given to ensure collection of sufficient stem cells for several transplants.
- Common side effects of high-dose chemotherapy and transplantation include nausea, vomiting, diarrhea, mucositis (inflammation of the lining of the mouth and digestive tract), and fatigue. In addition, because the high-dose chemotherapy attacks healthy, disease-fighting cells as well as cancerous cells, there is an increased risk of infection. Other possible, but infrequent side effects may include organ damage, particularly to the lungs, liver, and kidneys.
- Bisphosphonates
- Medicines that are used in the treatment of myeloma bone disease and are usually used in conjunction with other cancer therapy. Bone disease is common in multiple myeloma, with 85% of patients having bone problems.
- Bisphosphonates have been shown to:
- Help slow the advancement of bone disease
- Decrease bone pain
- Reduce fractures
- Improve overall survival (one large study)
- Bisphosphonates are also used in the treatment of bone metastases and hypercalcemia of malignancy (increased calcium levels in the blood). They are also used in other cancers where the bone is affected (e.g. breast cancer, prostate cancer).
- In addition, bisphosphonates are commonly used to treat osteoporosis (bone thinning) and are used in the treatment of a bone disease called Paget’s disease.
- Radiation therapy
- Radiation therapy is the use of high-energy particles or rays to damage cancer cells and prevent them from growing. Other names for radiation therapy include radiotherapy, x-ray therapy, and irradiation. Although some normal cells may be affected by radiation, the cells most susceptible to damage by radiation are fast-dividing cells such as those in the bone marrow and lining the digestive tract. Most normal cells appear to recover fully from the effects of the treatment. Low dose radiation therapy is often used to treat bone tumors in multiple myeloma patients
- Surgery
- Multiple myeloma surgery may be required to help control pain or retain function or mobility. These may include physical therapy, splinting of bones to prevent or treat fractures, or surgical procedures (minor or major) to repair fractures.
- The skeletal site most often affected by myeloma is the spine. Fractures of the bones of the spine (vertebrae) are associated with bone pain in more than half of patients when they are first diagnosed.
- New vertebral fractures occur in approximately 15 to 30 percent of patients with myeloma every year. The vertebrae become so weakened that they collapse upon themselves, resulting in a compression fracture. These fractures are very painful and can lead to a stooped posture, loss of height, immobility, and further fractures.
- Consequently, they have a significant impact on quality of life. Compression fractures, by reducing space in the chest and abdominal cavities, can also reduce lung capacity and cause loss of appetite.
- Alternative treatments
- Alternative treatments for multiple myeloma help patients deal with the side effects of myeloma and myeloma treatments. Multiple myeloma alternative therapy can include the following:
- Acupuncture
- Aromatherapy
- Massage
- Meditation
- Relaxation techniques
- Alternative treatments for multiple myeloma help patients deal with the side effects of myeloma and myeloma treatments. Multiple myeloma alternative therapy can include the following:
Where Can I Learn More???
- Learn more about this disease from the International Myeloma Foundation.
- Check out our cornerstone on this disease here.
