Multiple Myeloma - Symptoms, Stages, Causes, Treatment

Multiple myeloma is a complex and aggressive form of cancer involving the plasma cells in an individual’s bone marrow. It is rare cancer, with about 1 in 100,000 incidences in India. While there is no cure for the disease, healthcare providers can offer treatments to help individuals improve their quality of life and achieve remission. 

Treatment for multiple myeloma is not always necessary right away. Several options are available to control the disease for people who require treatment. The following blog discusses multiple myeloma symptoms, their causes, stages, diagnosis, and treatment options. Continue reading to learn everything about this type of cancer.

Multiple myeloma, or Kahler’s disease, is a type of blood cancer affecting plasma cells. These cells are a vital immune system component responsible for producing antibodies that help fight off infections.
However, in multiple myeloma, plasma cells become malignant and grow uncontrollably, crowding healthy bone marrow cells.

The excessive proliferation of abnormal plasma cells leads to the production of abnormal proteins called monoclonal antibodies or M proteins. These proteins can accumulate in various body parts, affecting bones, kidneys, and the body’s ability to make healthy blood cells and platelets.

Now that the multiple myeloma meaning is clear, it is important to know the types of the disease. There are several types and subtypes of multiple myeloma based on various factors.
Certain precancerous conditions can also lead to multiple myeloma. These types and conditions include:

1. Light Chain Myeloma: This subtype represents approximately 20% of cases. It develops when individuals make an incomplete immunoglobulin known as a light-chain antibody.
   These proteins can accumulate in the kidneys and damage them. 

2. Nonsecretory Myeloma: It is a rare form (2% to 4% of all cases) of multiple myeloma. The abnormal plasma cells do not produce significant amounts of M proteins or light chains, making diagnosing through typical laboratory tests challenging.
   A bone marrow biopsy can help diagnose nonsecretory myeloma. 

3. Solitary Plasmacytoma: It causes the formation of a tumour, usually in the bones. Having one of these tumours is called a solitary plasmacytoma. More than one tumour in different locations is a sign of multiple myeloma.
   While this type of myeloma generally responds well to treatment, it needs close monitoring.  

4. Immunoglobulin D (IgD) Myeloma: It is a rare type that only affects 1% to 2% of people with myeloma. Men below 60 are at a higher risk of getting it. 

5. Immunoglobulin E (IgE) Myeloma: This is the rarest form of multiple myeloma that tends to be aggressive. IgE quickly progresses to plasma cell leukaemia or spreads outside the bone marrow. 

6. Extramedullary Plasmacytoma: These tumours start in the body’s soft tissues outside the bone marrow. Generally, they develop in the throat, voice box, nose, and sinuses.
   Approximately 30% of people with this disease get multiple myeloma. 

7. Monoclonal Gammopathy of Undetermined Significance or MGUS: Multiple myeloma almost always starts as a relatively non-cancerous condition known as MGUS. It involves M proteins in the blood. 

8. Smouldering Multiple Myeloma (SMM): This is a precancerous form of multiple myeloma where more abnormal plasma cells are present in the bone marrow, but patients do not exhibit significant symptoms.
   Smouldering multiple myeloma may progress to active myeloma over time. About 50% of patients with SMM will be diagnosed with myeloma after five years. 

Multiple Myeloma Stages

Multiple myeloma is often classified into stages based on the extent of the disease and various clinical factors.
The Revised International Staging System (R-ISS) is the staging system most commonly used for multiple myeloma, which is based on the following levels: 

1. Albumin (a blood plasma protein made by the liver) in the blood 

2. Beta-2 microglobulin (a small protein found on the surface of the majority of cells in the body) in the blood

3. LDH (an enzyme that helps the body produce energy) in the blood

4. Cytogenetics (specific gene abnormalities) of the cancer

The three multiple myeloma stages are as follows:

1. Stage 1: Individuals with multiple myeloma in stage 1 have early disease. The stage is characterised by the following:

1. Albumin level of 3.5 g/dL or higher

2. Beta-2 microglobulin levels less than 3.5 mg/L

3. Normal LDH levels

4. Cytogenetics is not considered a high risk

2. Stage 2: Stage 2 of multiple myeloma is between the levels expected for stage 1 and stage 3. The cancer progresses in this stage, and the individual may begin experiencing symptoms. Test results for stage 2 show the following levels:  

1. Albumin levels less than 3.5 g/dL

2. Beta-2 microglobulin levels between 3.5 to 5.5 mg/L

3. Stage 3: This is the most advanced stage of the disease, with the greatest number of myeloma cells in the body. In this stage, the test results show the following levels:

1. Beta-2 microglobulin levels of 5.5 mg/L or above

2. LDH levels are high

3. Cytogenetics is considered a high risk

In the early stage of the disease, individuals may not experience any multiple myeloma symptoms. As cancer progresses, people with multiple myeloma may experience early symptoms, including bone pain (especially in the back or chest), fatigue and nausea. 

Individuals experience at least one of the four major symptoms, referred to by the acronym CRAB (calcium, renal failure, anaemia, bone damage). The CRAB multiple myeloma symptoms are as follows: 

1. Elevated Calcium Level Symptoms: The bones affected by multiple myeloma can leak calcium into the blood, leading to high calcium levels. This may cause symptoms like:

1. Nausea

2. Vomiting

3. Loss of appetite

4. Extreme thirst

5. Upset stomach

6. Constipation

7. Confusion

2. Renal (Kidney) Failure Symptoms: High levels of M protein in the body can lead to kidney damage or failure, causing symptoms such as:

1. A reduced amount of urine

2. Swelling in the ankles, legs, and feet

3. Excessive fatigue or drowsiness

4. Unexplained shortness of breath

5. Nausea

6. Pain or pressure in the chest

7. Confusion

8. Seizures

9. Coma

3. Anaemia Symptoms: Anaemia develops when cancer cells outnumber healthy red blood cells in the bone marrow. Symptoms of anaemia may include:

1. Fatigue

2. Dizziness

3. Irritability

4. Bone Damage Symptoms: When cancer cells invade the bone and bone marrow, they can lead to bone injuries and fractures, causing bone pain (particularly in the back, pelvis, ribs, and skull).
   Bone pain is often the first symptom people with multiple myeloma notice. 

Additional Symptoms

Besides the multiple myeloma CRAB criteria, other additional symptoms of the disease include:

1. Numbness or Weakness in Arms or Legs: This can occur due to the effect on bones in the spine, causing them to collapse and press on the spinal cord. 

2. Repeated Infections: Multiple myeloma weakens the immune system, making individuals more susceptible to infections.

3. Unexplained Weight Loss: A common symptom of multiple myeloma may result from a combination of factors, including reduced appetite and anaemia. 

4. Problems with Urination: This can result from multiple myeloma’s effect on kidney function. 

5. Unexplained Fever: People may develop a fever due to a bacterial infection. 

6. Easy Bruising and Bleeding: Abnormal plasma cells may prevent the body from producing enough platelets, making blood clotting difficult.

The exact multiple myeloma causes are not clear. However, multiple myeloma pathogenesis (the process by which the disease develops) begins in one abnormal plasma cell in the bone marrow.
This abnormal cell multiplies rapidly and accumulates, crowding out the healthy blood cells in an individual’s bone marrow. 

The myeloma cells also try to produce antibodies like the healthy blood cells. However, they produce abnormal antibodies that the body cannot use.
These abnormal antibodies (M proteins) build up in the body and cause problems like kidney damage. 

Multiple Myeloma Risk Factors

Multiple myeloma is a complex disease, and while the exact causes are not fully understood, several risk factors have been identified that may increase a person’s likelihood of developing the condition.
Here are some recognised risk factors for multiple myeloma:

1. Age: The risk of multiple myeloma increases with age. It is rare in individuals under 35, but the incidence rises significantly after age 65.

2. Gender: Men have slightly more chances than women to develop multiple myeloma.

3. Race: Multiple myeloma is more common in black people than in people of other races. 

4. Family History: A first-degree relative (parent or sibling) with multiple myeloma increases the risk of developing the disease.

5. Obesity: Being obese or overweight may increase a person’s risk of developing multiple myeloma. 

6. Environmental Factors: Some studies show a link between multiple myeloma and exposure to radiation or chemicals in fertilisers or pesticides. 

7. Monoclonal Gammopathy of Undetermined Significance or MGUS: It is a precursor condition for multiple myeloma characterised by abnormal plasma cells in the bone marrow.
   Individuals with MGUS have a higher risk of progressing to multiple myeloma over time.

Since only a few cases of multiple myeloma are linked to avoidable risk factors, there are currently no known methods for preventing the disease.
Research is ongoing to treat certain high-risk smouldering multiple myeloma and prevent them from becoming active multiple myeloma. 

However, there are certain precautions that individuals can take to reduce the risk of the disease:

1. Maintain a Healthy Body Weight: Being obese is linked to an increased risk of multiple myeloma. Therefore, individuals must maintain a healthy weight through regular physical activity and a balanced diet. 

2. Regular Health Check-Ups: Regular medical check-ups can help detect potential health concerns early. 

3. Quit Smoking: Cigarette smoking can increase the risk of various types of cancers. Quitting smoking can positively impact a person’s overall health.

Sometimes, doctors diagnose multiple myeloma accidentally during a blood test for other conditions. The condition can also be diagnosed if the doctor suspects multiple myeloma based on the signs and symptoms.
Tests used for multiple myeloma diagnosis include:

1. Blood Tests: Several laboratory blood tests are used to aid in the diagnosis of multiple myeloma. These tests include:

1. Complete Blood Count (CBC): The test measures the levels of red blood cells, white blood, and platelets. 

2. Blood Chemistry Test: The test shows the levels of creatinine (how well the kidneys work), albumin, calcium, and lactic dehydrogenase (LDH) in the blood. 

3. Quantitative Immunoglobulin Test: The test measures the levels of different antibodies (IgA, IgD, IgE, IgG, and IgM) in the blood. 

4. Serum Protein Electrophoresis: Multiple myeloma electrophoresis test looks for M protein in the blood.  

2. Urine Tests: Analysis of a urine sample can test for Bence Jones protein, which is an M protein detected in urine.  

3. Imaging Tests: Imaging tests are performed to evaluate bone damage, detect fractures, and assess the overall extent of the disease. Common imaging techniques used in multiple myeloma diagnoses include: 

1. X-rays: Multiple myeloma X-ray is used to look for bones damaged by the disease. Often doctors perform a series of X-rays that includes most of the bones. Multiple myeloma skull X-ray is also performed to look for lesions in the skull. 

2. Computed Tomography (CT) Scan: It takes X-rays from different angles to make detailed pictures of the organs. The test also helps guide a biopsy needle. 

3. Magnetic Resonance Imaging (MRI): The multiple myeloma radiology test creates detailed images of the bone and spine using radio waves and strong magnets. It may be used to look for plasmacytomas (single groups of abnormal plasma cells). 

4. Positron Emission Tomography (PET) Scan: This is another test to find plasmacytomas that cannot be seen on regular X-rays.

4. Bone marrow Biopsy and Aspiration: The doctor will perform a bone marrow biopsy to confirm multiple myeloma diagnosis. A small sample of bone marrow is taken from the hipbone or another suitable site using a needle. 
   The sample is then examined under a microscope to evaluate the presence of abnormal plasma cells and assess multiple myeloma pathology outlines. 

5. Genetic and Cytogenetic Testing: Special tests, such as immunohistochemistry, flow cytometry, and fluorescent in situ hybridisation (FISH), may be conducted on the bone marrow sample to identify specific genetic abnormalities or mutations associated with multiple myeloma.
   These tests can help guide treatment decisions and provide insights into the prognosis.

Diagnostic Criteria for Multiple Myeloma

Multiple myeloma diagnostic criteria, as per the International Myeloma Working Group (IMWG), include:

1. Malignant Plasma Cells: Presence of at least 10% or more malignant plasma cells in the bone marrow or biopsy sample or evidence of a biopsy-proven plasmacytoma.

2. Any one or more of the following events:

1. End-Organ Damage: Presence of one or more of the following multiple myeloma CRAB criteria:

1. C: Calcium elevation (serum calcium level > 1 mg/dL more than the upper limit of normal or > 11 mg/dL).

2. R: Renal failure (creatinine clearance < 40 mL per minute or serum creatinine > 2 mg/dL).

3. A: Anaemia (haemoglobin level > 2 g/dL below the lower limit of normal level or a haemoglobin level < 10 g/dL).

4. B: Bone damage (one or more osteolytic lesions on imaging studies).

2. Clonal bone marrow plasma cells ≥ 60% with or without CRAB.

3. Involved/uninvolved serum-free light chain ratio ≥ 100.

4. One or more focal lesions on MRI (each > 5 mm in size).

How to Prepare for Doctor’s Consultation?

Preparing for a consultation appointment for multiple myeloma can help patients ensure that they make the most of their time with the healthcare provider.
Here are some steps to help them prepare for the appointment:

1. Write Down Symptoms: Patients must list the symptoms they experience, including specific concerns, when they started, or any changes.

2. Share Medical History: Prepare a summary, including any past illnesses, surgeries, or ongoing medical conditions. The doctor will want to know if the patient has been diagnosed with other plasma disorders like MGUS.  

3. Make a List of Medications: Patients must mention their medications, vitamins, supplements, or herbal remedies.

4. Prepare a List of Questions: Patients must note any questions about multiple myeloma, its diagnosis, treatment options, side effects, and prognosis they want to ask the doctor. 

5. Bring a Friend or Family Member: It is recommended to bring a friend or family member to the appointment. They can provide emotional support, help remember important details, and take notes during the discussion.

What to Expect from the Doctor?

During a multiple myeloma consultation appointment, the healthcare provider will likely ask several questions to gather information about the patient’s medical history, symptoms, and overall health.
While the specific questions might vary depending on the individual and the healthcare provider’s approach, here are some common questions one can expect:

1. What symptoms are you experiencing?

2. When did you first notice these symptoms?

3. Have these symptoms changed over time?

4. Do you experience bone pain? If yes, where?

5. Have you noticed any unexplained weight loss or fatigue?

6. Are you experiencing frequent infections, like pneumonia, sinusitis, or skin infections?

7. Have you observed any changes in your urinary habits or kidney-related symptoms?

8. Have you been previously diagnosed with any other medical conditions? 

9. Is there a family history of plasma disorders like MGUS or multiple myeloma?

10. Are you taking any medications, vitamins, or supplements?

Questions to Ask the Doctor

During a consultation appointment for multiple myeloma, patients must ask questions to understand better their condition, treatment options, and prognosis. Here are some questions they may consider asking the doctor:

1. What is the cause of my symptoms?

2. What kind of tests do I need for diagnosis?

3. Are there any restrictions to be followed before diagnostic tests?

Questions to ask the specialist after a diagnosis include:

1. What stage is my multiple myeloma? 

2. What does this mean for my prognosis?

3. Is multiple myeloma curable? 

4. What is the goal of multiple myeloma treatment?

5. What are the recommended treatment options for my specific case?

6. What are the risks and benefits associated with each treatment option?

7. How can I manage or alleviate treatment side effects?

8. How will treatment affect my daily life and quality of life?

9. Am I a candidate for a stem cell transplant?

10. If the first treatment is unsuccessful, what will be my next option?

11. How often will I need to come for follow-up visits or tests?

12. What signs or symptoms should I watch for that require immediate medical attention?

13. Would seeking a second opinion about my diagnosis or treatment plan be beneficial?

Multiple myeloma treatment depends on various factors, including the stage and aggressiveness of the disease, the presence of symptoms, the individual’s overall health, and personal preferences.
Treatment goals can include managing symptoms, controlling disease progression, and improving quality of life. The following are some common treatment options for multiple myeloma:

1. Observation: In some cases, close monitoring with periodic blood and urine tests, without immediate treatment, may be recommended if the disease is asymptomatic or progressing slowly.

2. Chemotherapy: Multiple myeloma chemotherapy drugs, often used in combination, kill or control the growth of myeloma cells. High doses of chemotherapy drugs are also given before a bone marrow transplant.
   These medications may be given intravenously or as a pill. 

3. Targeted Therapy: They are drugs specifically targeting certain proteins or pathways involved in the growth and survival of myeloma cells.
   Examples include drugs such as bortezomib and carfilzomib, administered intravenously or through a vein in the arm. 

4. Immunotherapy: It uses the body’s immune system to recognise and destroy myeloma cells.
   Multiple myeloma medications for immunotherapy may include monoclonal antibodies like daratumumab, siltuximab, and elotuzumab.

5. Corticosteroids: Medications like dexamethasone and prednisone help regulate the immune system to kill cancer cells and reduce inflammation. They can be taken intravenously or as a pill. 

6. Radiation Therapy: It uses strong beams of energy to target and kill myeloma cells in specific areas affected by these cells, such as bone lesions causing pain or potential fractures.

7. Bone Marrow Transplant: A bone marrow transplant (stem cell transplant) may be recommended for eligible patients. The procedure replaces the diseased bone marrow with healthy blood-forming cells.
   Before the procedure, the patient is treated with high doses of chemotherapy. 

   Doctors typically recommend autologous stem cell transplantation (using the patient’s own stem cells). In rare cases, patients may receive an allogeneic stem cell transplantation (healthy plasma stem cells from a donor).

8. Supportive Care: Supportive care plays a crucial role in managing symptoms, controlling pain, preventing infections, and addressing the side effects of treatment.
   This may include pain medications to manage significant bone pain and antibiotics to clear up infections caused by a weakened immune system. 

Please Note: The selection of the treatment approach is based on the patient’s overall health and the treating doctor’s opinion. 

Cost of Multiple Myeloma Treatment

The cost of multiple myeloma treatment depends on several factors, including the type of myeloma, stage of myeloma, patient’s age, patient’s comorbidities, hospital type and location, doctor’s expertise, insurance coverage and much more.

To know the exact cost of the multiple myeloma treatment, one must visit their healthcare professional. However, the table provided also provides the cost of various treatment modalities for multiple myeloma.

Multiple Myeloma Survival Rate

Multiple myeloma survival rates can vary widely depending on various factors, including the stage of the disease, age of the patient, overall health, and response to treatment.
Survival rates are often given as five-year relative survival rates, which indicate the percentage of people alive five years after diagnosis compared to the general population.

According to the American Cancer Society, the overall 5-year survival rate for multiple myeloma is as follows:

Multiple myeloma can lead to various complications due to the effects of the disease on the body. Here are some common complications associated with multiple myeloma:

1. Bone Problems: Multiple myeloma often affects the bones, destroying and weakening the bone. This can result in bone pain, thinning bones, and fractures. 

2. Anaemia: The abnormal plasma cells in multiple myeloma can crowd out healthy blood cells, decreasing red blood cell production and causing anaemia. 

3. Kidney Problems: The kidneys filter waste and toxins. Myeloma cells make M proteins that block this filtering process, leading to kidney damage and impaired kidney function.

4. Frequent Infections: Abnormal plasma cells can crowd out healthy white blood cells that fight infections.
   This increases the risk of infections, including bacterial infections, particularly pneumonia. 

5. Blood Clotting: Abnormal plasma cells can also crowd out platelets (cells that help the blood clot) from the bone marrow, leading to problems with blood clotting. 

6. Amyloidosis: In some cases, abnormal proteins (amyloid proteins) produced by the myeloma cells can build up in various organs and tissues, causing amyloidosis.

7. Hypercalcemia: Multiple myeloma can cause damaged or weakened bones to release high calcium levels in the blood, known as hypercalcemia.

8. Hyperviscosity Syndrome: M proteins thicken the blood. This makes the heart work harder to pump blood throughout the body. 

9. Cryoglobulinemia: Multiple myeloma can lead to a condition called cryoglobulinemia. It makes the proteins in the blood clump together in cold temperatures. 

When to See a Doctor?

Patients should visit a doctor if they experience any multiple myeloma symptoms that do not go away. Although other conditions can also cause these symptoms, seeking medical evaluation for a proper diagnosis is essential.
Symptoms that may require medical attention include:

1. Unexplained bone pain

2. Frequent infections

3. Fatigue and weakness

4. Bone fractures

Sometimes, multiple myeloma cancer can cause complications even before being diagnosed. In such a situation, patients should see their doctors right away. These complications may include:

1. Spinal cord compression

2. Hyperviscosity

3. Kidney damage and failure

Patients with multiple myeloma can have difficulty with eating. The disease symptoms or treatment side effects can make it hard to eat as much as they used to.
While no specific diet can cure multiple myeloma, maintaining a healthy and balanced diet can provide the right nutrients to nourish the body. Some dietary recommendations are as follows:

Foods to Eat

1. Greens: Fruits and vegetables are rich in antioxidants that help rebuild the body.
   Consuming cooked fruits and vegetables can also fight constipation and reduce the chances of infection. 

2. Iron: Cancerous cells in the body can lead to anaemia, causing problems such as weakness, fatigue, and feeling cold. Iron-rich foods help patients feel less tired and make more healthy red blood cells.
   Good iron sources include lean red meat, broccoli, bell peppers, tropical fruits, etc. 

3. Fibre: Consuming fibre-rich foods can help promote regular bowel movements and prevent constipation.
   Patients must consider including whole grains, fruits, vegetables, legumes, and nuts in their diet.

4. Bland Foods: If individuals are dealing with diarrhoea, they may have to eat a low-fibre diet called the BRAT diet (Bananas, Rice, Applesauce, Toast). It will also help to stay hydrated by drinking plenty of water.
   Patients with mouth sores should eat easy-to-swallow foods and avoid spicy food that may irritate their tongue and mouth. 

Foods to Avoid

Since multiple myeloma makes the immune system weaker, individuals with this condition must avoid any food that can make them sick, including:

1. Unwashed fruits and vegetables

2. Runny eggs

3. Raw meat or fish

4. Sushi 

5. Unpasteurised drinks

Multiple myeloma is a complex and potentially serious blood cancer affecting plasma cells in the bone marrow. It can cause various symptoms and complications, requiring timely diagnosis and appropriate treatment. 

While multiple myeloma prognosis and survival rates vary depending on individual factors, advancements in treatment options have improved outcomes for many patients. 

At HexaHealth, our dedicated team of healthcare professionals is committed to supporting individuals with multiple myeloma. We provide comprehensive care, from initial diagnosis to ongoing management. Contact us to learn more about our services and how we can assist you in your journey towards better health. 

Suggested Reads