Multiple Myeloma - Symptoms, Stages, Causes, Treatment

It is a condition where a type of blood cell, called a plasma cell, multiplies uncontrollably. 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 ability of the body to make healthy blood cells and platelets. If there's just one lump, it's called a plasmacytoma. If there are many lumps, it's known as multiple myeloma.

When bones become weak or damaged, two types of bone cells stop working together as they should. Normally, osteoblasts build new bone, and osteoclasts break down old bone. However, in this condition, the cancer cells cause osteoclasts to break down bone much faster than usual, leading to bone damage.

Below are the types of multiple myeloma:

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 this condition.
   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 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: It 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 in which more abnormal plasma cells are present in the bone marrow, but patients do not exhibit significant symptoms.
   Smouldering may progress to active myeloma over time. About 50% of patients with SMM will be diagnosed with myeloma after five years. 

Multiple Myeloma Stages

It 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: 

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

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

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

• 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:

• Albumin level of 3.5 g/dL or higher

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

• Normal LDH levels

• 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:  

• Albumin levels less than 3.5 g/dL

• 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:

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

• LDH levels are high

• Cytogenetics is considered a high risk

In the early stage of the disease, individuals may not experience any 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 this condition can leak calcium into the blood, leading to high calcium levels. This may cause symptoms like:

• Nausea

• Vomiting

• Loss of appetite

• Extreme thirst

• Upset stomach

• Constipation

• 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:

• A reduced amount of urine

• Swelling in the ankles, legs, and feet

• Excessive fatigue or drowsiness

• Unexplained shortness of breath

• Nausea

• Pain or pressure in the chest

• Confusion

• Seizures

• Coma

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

• Fatigue

• Dizziness

• 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: It weakens the immune system, making individuals more susceptible to infections.

3. Unexplained Weight Loss: A common symptom 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.

"I recently cared for a patient battling multiple myeloma, a cancer that affects plasma cells in the bone marrow. The journey was tough, with periods of intense treatment and uncertainty, but seeing my patient respond to therapy and regain their strength was incredibly moving.

Multiple myeloma can be a relentless disease, but with advancements in treatment, there is hope and a path forward. Witnessing my patient embrace life again with renewed optimism reminded me of the resilience of the human spirit. Every victory in this fight, no matter how small, is a powerful testament to the courage of those who face this diagnosis."

- Dr Abhishek Gulia
Oncologist

The exact 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

It 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: It 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 myeloma and exposure to radiation or chemicals in fertilisers or pesticides. 

7. Monoclonal Gammopathy of Undetermined Significance or MGUS: It is a precursor condition 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 this disease 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 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 this disease accidentally during a blood test for other conditions. The condition can also be diagnosed if the haemotologist 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 the condition. 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 the diagnoses include: 

1. X-rays: Multiple myeloma X-ray is used to look for bones damaged by the disease. Often oncologists perform a series of X-rays that includes most of the bones. The 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.

Multiple Myeloma Diagnostic Criteria

The 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 can help you get the most out of your appointment. Note your symptoms, when they started, and any changes.

Put together your past health issues, surgeries, and any ongoing conditions, especially if you've had plasma disorders like MGUS. Include all medications, vitamins, and supplements. Write down any questions about diagnosis, treatment, or side effects.

What to expect from the doctor?

During a consultation for multiple myeloma, the haemotologist doctor will likely ask about your symptoms, when they started, and if they've changed over time. Common questions include:

• Are you experiencing bone pain? If so, where?

• Have you noticed any unexplained weight loss or fatigue?

• Do you get frequent infections, like pneumonia or sinus problems?

• Have you had any changes in urination or kidney issues?

• Do you have any other medical conditions?

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

• Are you taking any medications, vitamins, or supplements?

Questions to Ask the Doctor

After a myeloma diagnosis, consider asking:

• What stage is my myeloma, and what does it mean for my outlook?

• Can multiple myeloma be cured?

• What treatment options are best for me?

• What are the risks and benefits of each treatment?

• How can I handle or reduce side effects?

• What if the first treatment doesn't work?

• How often will I need follow-up visits or tests?

• What symptoms should prompt immediate medical attention?

Treatment for multiple myeloma depends on factors like the disease stage, severity, symptoms and overall health. The goals are to manage symptoms, control the disease, and improve quality of life. Common treatment options include:

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

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.

4. Immunotherapy: The immune system of the body recognises and destroy myeloma cells.

5. Corticosteroids: Multiple myeloma 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 radiation 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: This treatment replaces sick bone marrow with healthy cells. Patients first receive high-dose chemotherapy to prepare for the transplant.

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

Multiple Myeloma Treatment Cost

The cost of multiple myeloma treatment in India varies based on factors like the type and stage of the disease, age, other health conditions, hospital and doctor, and insurance coverage.

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.

The R-ISS staging system for multiple myeloma shows survival rates for different stages:

• Stage I: 82% survival rate over five years and 55% progression-free rate.

• Stage II: 62% survival rate and 36% progression-free rate.

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

1. Bone Issues: It can weaken and damage bones, leading to pain, thinning, and fractures.

2. Anaemia: It reduces healthy blood cells, causing tiredness and weakness.

3. Kidney Problems: Myeloma cells can block the ability of the kidney to filter waste, leading to kidney damage.

4. Frequent Infections: It lowers the number of healthy white blood cells, increasing infection risk.

5. Blood Clotting Issues: It can affect platelets, causing problems with blood clotting.

6. High Calcium Levels: Weak bones can release excess calcium into the blood, leading to hypercalcemia.

When to see a doctor?

Patients should visit an oncologist 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:

• Unexplained bone pain

• Frequent infections

• Fatigue and weakness

• Bone fractures

For people with multiple myeloma, eating well can help support their health. These precautions help protect a weakened immune system and maintain health.

Foods to Eat:

• Greens: Fruits and vegetables are packed with antioxidants and can help with digestion and infections. Cooked options are easier on the stomach.

• Iron-rich foods: Help combat anaemia and boost energy. Good sources include lean red meat, broccoli, bell peppers, and tropical fruits.

• Fibre: Helps with digestion and prevents constipation. Include whole grains, fruits, vegetables, legumes, and nuts.

• Bland Foods: If dealing with diarrhoea, try the BRAT diet (Bananas, Rice, Applesauce, Toast) and drink plenty of water. For mouth sores, stick to soft, non-spicy foods.

Foods to Avoid:

• Unwashed Fruits and Vegetables

• Runny Eggs

• Raw Meat or Fish

• Sushi

• Unpasteurized 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. 

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