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Multiple Myeloma
Understanding Multiple Myeloma: Symptoms, Diagnosis, Stages, and Treatment Near You at RCCA
Multiple myeloma (MM) is a blood cancer that begins in the plasma cells of the bone marrow. If you or a loved one has been diagnosed with multiple myeloma, comprehensive treatment is available at Regional Cancer Care Associates. As one of the nation’s largest networks of oncology specialists, RCCA provides cutting-edge therapies and care for multiple myeloma, along with treatment for other cancers and benign blood disorders, at more than 20 locations near you throughout New Jersey, Connecticut, Massachusetts, and the Washington, D.C., area. Learn more about multiple myeloma, its symptoms and stages, and the treatment options available.
Key Takeaways
- Multiple myeloma is a type of blood cancer that originates in the plasma cells of the bone marrow. The plasma cells turn into cancerous cells that grow uncontrollably, producing an abnormal protein called M protein that damages organs and bones.
- The hallmark symptoms of multiple myeloma include the CRAB criteria: calcium elevation, renal impairment, anemia, and bone damage. They also include extreme fatigue, frequent infections, weakness, peripheral neuropathy, and more.
- Treating multiple myeloma often involves using a combination of targeted therapies, immunomodulators, corticosteroids, and monoclonal antibodies. Autologous stem cell transplants and other immunotherapies may also be used.
- Regional Cancer Care Associates provides high-quality care for patients with multiple myeloma in New Jersey, Connecticut, Massachusetts, and the Washington, D.C., area.
What Is Multiple Myeloma?
Multiple myeloma is a blood cancer that forms in plasma cells in the bone marrow. In healthy bone marrow, plasma cells create antibodies to protect the body from infection. In multiple myeloma, plasma cells transform into cancerous cells that grow uncontrollably, reducing the number of normal infection-fighting cells. The malignant plasma cells produce an abnormal protein called M protein, which damages organs and bones.
Multiple myeloma is rare, accounting for about 1.8% of all new cancer diagnoses. According to the American Cancer Society, the average lifetime risk of getting multiple myeloma is less than 1% for people living in the United States.
How Multiple Myeloma Differs from Leukemia and Lymphoma
Multiple myeloma, leukemia, and lymphoma are all blood cancers, but they differ in important ways. Multiple myeloma impacts plasma cells in the bone marrow, while leukemia primarily affects white blood cells in the bone marrow and blood, and lymphoma affects lymphocytes in the lymphatic system.
What Are MGUS and Smoldering Myeloma?
Monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma are precursor conditions to multiple myeloma. They occur before full-blown MM and may progress to MM. Both conditions are asymptomatic and do not require active treatment. In distinguishing these conditions from MM, hematologists consider factors including blood levels of M-protein and the number of abnormal plasma cells in the bone marrow.
Understanding Multiple Myeloma Symptoms: The CRAB Criteria
Multiple myeloma causes cancerous plasma cells to grow inside the bone marrow, resulting in the gradual emergence of systemic symptoms. These symptoms can be vague in nature, and often are attributed to other causes, such as aging, arthritis, or muscle strain. However, as multiple myeloma progresses, more-definitive symptoms encompassed by the CRAB criteria appear. These include:
C: Calcium Elevation
People often experience elevated calcium levels, a condition known as hypercalcemia. This occurs because the cancer activates osteoclasts, the cells that break down bone. Bone tissue is dissolved much faster than new bone can form, so it releases large amounts of stored calcium into the bloodstream.
Levels of serum calcium > 11 mg/dL or more than 1 mg/dL above normal are considered hypercalcemic. Hypercalcemia can result in various symptoms, including excessive thirst, frequent urination, constipation, and confusion.
R: Renal Impairment or Failure
Multiple myeloma can also lead to renal (kidney) impairment or failure. This is because myeloma proteins cause a toxic buildup of abnormal antibody fragments that clog the filtering units and poison kidney cells.
Kidney impairment is diagnosed when creatinine clearance tests are < 40 mL/min or serum creatinine is > 2 mg/dL. Symptoms of kidney involvement include:
- Fatigue
- Swelling in the legs or feet
- Foamy or frothy urine
- Changes in urination frequency
- Nausea
- Loss of appetite
- Intense thirst
A: Anemia
Multiple myeloma can result in anemia, which is defined as a hemoglobin value < 10 g/dL. This can occur as abnormal plasma cells multiply and crowd the bone marrow, limiting the production of healthy red blood cells. Symptoms of anemia include fatigue, shortness of breath, pallor, weakness, dizziness, irregular heartbeat, and more.
B: Bone Damage
Multiple myeloma can also cause bone damage, including bone lesions and resultant pain, because it disrupts the body’s natural bone-remodeling cycle. Bone problems caused by MM typically affect the back, hips, ribs, or skull.
To detect bone lesions and damage, imaging such as X-rays, computed tomography (CT) scans, and magnetic resonance imaging (MRI) scans are often used. They can identify osteolytic lesions, such as bone thinning or fractures, that occur with MM.
Additional Symptoms Beyond CRAB
Along with the telltale CRAB symptoms, patients with multiple myeloma may experience other signs of the condition. They include:
- Frequent infections, due to impaired immunity
- Peripheral neuropathy (numbness, tingling, or burning in the hands and feet)
- Weakness
- Amyloidosis (protein deposits in organs)
- Easy bleeding or bruising
- Extreme fatigue
How Is Multiple Myeloma Diagnosed?
A person must meet specific criteria to be diagnosed with multiple myeloma. He or she must:
- Have ≥ 10% clonal plasma cells in a bone marrow biopsy or a confirmed tumor (plasmacytoma)
- Have M-protein (myeloma protein) present in the serum or urine
- Experience at least one of the CRAB criteria
The standard diagnostic workup for multiple myeloma typically includes:
- Blood tests: These include a complete blood count (CBC) to test for anemia, a comprehensive metabolic panel (CMP) to check kidney function and calcium levels, and serum free light chain (FLC) assays to measure ratios of specific proteins. Serum protein electrophoresis (SPEP) will also be ordered to identify the presence of M-protein in the blood.
- Urine tests: These include a 24-hour urine protein electrophoresis (UPEP) test to measure monoclonal immunoglobulins, which indicate MM when elevated.
- Bone marrow biopsy and aspiration: The doctor will collect a liquid and solid sample from a bone to determine the percentage of abnormal plasma cells. If there are 10% or more clonal plasma cells in the biopsy, a diagnosis of MM is more likely.
- Imaging: Imaging scans are often ordered to check for bone lesions or other bone damage, which is consistent with the CRAB criteria. Scans used include low-dose whole-body CTs, MRIs, or positron emission tomography (PET) scans.
Using the information gathered from these tests, a diagnosis of multiple myeloma can be confirmed or ruled out.
What Are the Stages of Multiple Myeloma?
When multiple myeloma is diagnosed, it is given a stage, typically using the Revised International Staging System (R-ISS). This system assesses four main blood and genetic markers:
- Beta-2 microglobulin (B2M)
- Albumin
- Lactate dehydrogenase (LDH)
- Cytogenetics (DNA changes)
Stage I is when B2-M is under 3.5 mg/L and albumin is 3.5 g/dL or higher. It is also marked by normal LDH levels and standard-risk chromosomal features. It typically has a favorable prognosis. Stage II is an intermediate stage where the levels are between Stage I and Stage III. Stage III indicates advanced and aggressive disease, characterized by a high B2-M level over 5.5 mg/L, along with high LDH levels or high-risk genetic abnormalities.
This information is used to inform treatment plans and to determine whether treatment should start immediately or if the cancer can be monitored for an initial period.
| Stage I | Stage II | Stage III | |
| Key Markers |
|
Levels are in between Stage I and Stage III markers |
|
| Median Survival |
62 months |
44 months |
29 months |
| Treatment Intensity | Depends on whether the disease is active or smoldering (asymptomatic) | Typically intensive, multi-drug therapies | Multi-step, aggressive approach |
What Are the Treatment Options for Multiple Myeloma?
The treatment of multiple myeloma is highly individualized. The approach chosen will depend on a variety of factors, including the stage of cancer, the patient’s overall health, and his or her symptoms. Options include:
Triplet or Quadruplet Drug Combination Therapy
First-line treatment (induction therapy) for newly diagnosed multiple myeloma typically involves a three-drug (triplet) or four-drug (quadruplet) combination. These drug regimens help reduce the tumor burden, reverse organ damage, and achieve the best outcomes possible. They also help to prepare eligible patients for an autologous stem cell transplant (ASCT). The drugs used for MM treatment include:
Proteasome Inhibitors
Proteasome inhibitors (PIs) target the overproduction of M proteins. There are three main PIs used in multiple myeloma treatment:
- Bortezomib, which is given via injection
- Carfilzomib, which is given intravenously
- Ixazomib, which is an oral pill taken at home
Common side effects of PIs include gastrointestinal upset, such as nausea and diarrhea; fatigue; lowered blood platelet counts; and potential neuropathy.
Immunomodulatory Drugs (IMiDs)
Immunomodulatory drugs (IMiDs) are pill-based therapies used to treat multiple myeloma. They target and attack tumor cells while also boosting the patient’s immune system to fight the cancer. IMiDs are also helpful for protecting bones from the weakening that MM can cause. They block the cells that break down bones and increase the cells that build new bone.
There are three main types of IMiDs used for MM:
- Lenalidomide
- Pomalidomide
- Thalidomide
Although IMiDs are very effective, patients need to be monitored for the side effects they can cause, including blood clots, low blood counts, and birth defects in pregnant women.
Monoclonal Antibodies
Monoclonal antibodies are lab-made proteins that imitate natural immune system defenses. To treat multiple myeloma, they target specific proteins on the surface of cancer cells to destroy them. They can either flag the cells so the immune system will attack the cancer, directly kill the cancer cells themselves, or boost the immune system to detect the cancer cells and strengthen infection-fighting cells. There are three main types of monoclonal antibodies used in MM treatment:
- Daratumumab
- Elotuzumab
- Isatuximab
Side effects of these drugs include infusion reactions, such as fever or chills, low blood cell counts, fatigue, and infections.
Autologous Stem Cell Transplant (ASCT)
After patients complete induction therapy, they may be eligible for an autologous stem cell transplant (ASCT). This process involves removing the patient’s healthy stem cells, administering a high dose of chemotherapy to destroy cancer cells, and reinfusing the patient’s healthy stem cells.
After the transplant, patients typically need maintenance therapy to control any remaining myeloma cells and extend remission. Although ASCT is not a cure for multiple myeloma, it is an effective tool for achieving deep remissions and prolonging progression-free survival.
CAR-T Cell Therapy
If patients are experiencing relapsing or refractory multiple myeloma, CAR-T cell therapy may be used. It involves extracting T-cells – key components of the immune system — from the patient’s body, genetically modifying them to target the BCMA protein on myeloma cells, and reinfusing them into the patient’s body. Once they’re infused, these cells work to hunt down and attack cancer cells. There are two primary options for CAR-T cell therapy at this time:
- Ciltacabtagene autoleucel, which is for patients who have had at least one prior line of therapy
- Idecabtagene vicleucel, which is for those with at least two prior lines of therapy
CAR-T cell therapy causes a powerful immune response, so patients must be closely monitored for side effects, including cytokine release syndrome (CRS), neurologic toxicities, and cytopenias (low blood counts).
Bispecific Antibodies
Bispecific antibodies are among the newest multiple myeloma therapies. They are a type of immunotherapy that attaches to two different targets, bringing them together. The first target is the protein BCMA or GPRC5D on the surface of myeloma cells. The second is theCD3 receptor on the patient’s T-cells. By bringing the cancer cell and the immune cell together, the T-cell is activated to destroy the tumor. These therapies are mostly used for patients with relapsed, refractory, or heavily pre-treated MM. They include:
- Teclistamab, which targets BCMA
- Talquetamab, which targets GPRC5D
The risks of bispecific antibodies include cytokine release syndrome (CRS), neurologic toxicities, and infections.
Drug Class Chart
Drug Class | Example Drugs | Method of Administration | Key Side Effects |
Proteasome Inhibitors |
| Subcutaneous Injection, intravenous (IV) infusion, or oral pill |
|
Immunomodulatory Drugs (IMiDs) |
| Oral pill |
|
Monoclonal Antibodies |
| Intravenous infusion or subcutaneous injection |
|
CAR-T Cell Therapy |
| IV infusion |
|
Bispecific Antibodies |
| Intravenous infusion or subcutaneous injection |
|
Find Comprehensive Multiple Myeloma Care Near You in NJ, CT, MA, and the Washington, D.C., Area
A diagnosis of multiple myeloma can be overwhelming. Fortunately, high-quality treatment is available at Regional Cancer Care Associates (RCCA). We have an expert team of hematologist-oncologists with myeloma subspecialty experience, and we also provide access to clinical trials for multiple myeloma, including studies evaluating CAR-T cell therapy and bispecific antibodies. We have more than 20 locations near you across New Jersey, Connecticut, Massachusetts, and the Washington, D.C., area, providing convenient care close to home. To learn more about multiple myeloma treatment or to discuss clinical trial eligibility, contact us today.
Frequently Asked Questions About Multiple Myeloma
What is multiple myeloma?
Multiple myeloma is a form of blood cancer that originates in the plasma cells in bone marrow. These plasma cells transform into cancerous cells that grow out of control and produce an abnormal protein called M protein, which leads to organ and bone damage.
Is multiple myeloma curable?
Multiple myeloma is considered incurable, but it is highly treatable.
What are the CRAB criteria for multiple myeloma?
The CRAB criteria for multiple myeloma refer to the symptoms that patients experience. Physicians look for these symptoms as part of the diagnostic process for MM. CRAB stands for:
- Calcium elevation
- Renal impairment
- Anemia
- Bone damage
What are the symptoms of multiple myeloma?
The symptoms of multiple myeloma include the CRAB criteria: calcium elevation, renal impairment, anemia, and bone damage. Symptoms can also include extreme fatigue, frequent infections, weakness, peripheral neuropathy, amyloidosis, and easy bleeding or bruising.
What is the difference between MGUS and multiple myeloma?
Monoclonal gammopathy of undetermined significance (MGUS) is a benign, asymptomatic precursor condition that does not cause organ damage. Multiple myeloma is a progressive, malignant blood cancer that causes damage to bones, kidneys, and blood cells. MGUS can turn into MM over time.
What are the treatment options for multiple myeloma?
The treatment options for multiple myeloma include a combination of targeted therapies, immunomodulators, corticosteroids, and monoclonal antibodies. For certain patients, autologous stem cell transplants are used.
What is CAR-T cell therapy for myeloma?
CAR-T cell therapy is an innovative form of immunotherapy that can be used to treat multiple myeloma. It harnesses the capabilities of the patient’s own immune system to train it to hunt down and destroy multiple myeloma cells.
Is multiple myeloma a bone cancer?
No, multiple myeloma is considered a blood cancer because it affects the plasma cells (a type of white blood cell) in the bone marrow, not the bone itself.
Regional Cancer Care Associates — A “whole life” approach to cancer care
At Regional Cancer Care Associates (RCCA), we take a comprehensive, “whole-life” approach, treating you as a whole person — not just your disease. We treat your cancer in an individualized and medically advanced manner. At RCCA, you’ll be diagnosed, treated and cared for by nationally-recognized experts who are close to your home.
You can schedule an appointment or get more information by calling (844) 346-7222. You can also schedule an appointment by calling the RCCA location near you.
Physicians SPECIALIZED IN Multiple Myeloma
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