Multiple Myeloma

Multiple Myeloma

Click here to read about staging of multiple myeloma


Multiple myeloma is a type of blood cancer involving plasma cells of the blood. Plasma cells are a type of white blood cell, which is normally responsible for making antibodies. In India as per ICMR data,Multiple myeloma is the second most common hematological malignancy after non hodgkins lymphoma and it accounts for 15% of all hematological malignancies.


Overview

Due to advancements in modern medicine, the disease is considered as a treatable disease but not a curable disease. Presently chemotherapy remains as the mainstay of treatment. With the advent of Bone Marrow Transplant and Stem Cell Transplant, these have taken up an important place in the treatment protocols. But still, chemotherapy or induction therapy is essential before and later for transplant eligible and only therapy for transplant ineligible.

The median age of occurence of the disease in various single institute data across India reports at around 52-61 years.

The underlying mechanism involves abnormal plasma cells producing abnormal antibodies which can cause kidney problems and overly thick blood.[1] The plasma cells can also form a mass in the bone marrow or soft tissue.[1] When only one mass is present, it is known as a plasmacytoma while more than one is known as multiple myeloma.[1]

Multiple myeloma effects the three major components of our body:

  • Blood
    • The growing number of myeloma cells can interfere with the production of all types of blood cells
    • A reduction in the number of white blood cells can increase the risk of infection, whereas decreased red blood cell production can result in anemia
    • A reduction in platelets can prevent normal blood clotting. In addition, high levels of M protein and light chains (portions of immunoglobulin molecules, also known as Bence Jones proteins), crowd out normal functioning immunoglobulins and “thicken” the blood, causing additional symptom
  • Kidney
    • Excess M protein and calcium in the blood overwork the kidneys as they filter blood and causes damage to the kidneys
  • Bone
    • First, the cells gather to form masses in the bone marrow that may disrupt the normal structure of the surrounding bone
    • Myeloma cells secrete substances that interfere with the normal process of bone repair and growth

Risk Factors

Monoclonal gammopathy of undetermined significance (MGUS) increases the risk of developing multiple myeloma. MGUS transforms to multiple myeloma at the rate of 1% to 2% per year, and almost all cases of multiple myeloma are preceded by MGUS

Smoldering multiple myeloma increases the risk of developing multiple myeloma. Individuals diagnoses with this pre-malignant disorder develop multiple myeloma at a rate of 10% per year for the first 5 years, 3% per year for the next 5 years, and then 1% per year.

Both exposure (environmental or occupational) to particular agents & an individual’s susceptibility to these agents are thought to contribute to one’s risk of developing multiple myeloma

Risk Factors
Family History
Alcohol consumption has been linked to increase risk of multiple myeloma
Obesity:It is estimated that with each increase of body mass index by 5 points increases the risk by 11%
Sudden Weight Loss

Symptoms

Because many organs can be affected by myeloma, the symptoms and signs vary greatly

Some of the more common symptoms of myeloma can be remembered as

Symptoms
CRAB: C = calcium (elevated), R = renal (kidney) failure, A = anemia, B = bone lesions
Opportunistic infections (e.g., pneumonia)
Unexplained Weight loss
Joint and Bone Pain
Getting Tired /exhausted/Fatigue very quickly without any explanation
Neurological symptom (e.g., weakness, confusion, and fatigue)

Diagnosis

Apart from Biopsy and Imaging scans, multiple myeloma is confirmed based on blood and urine tests to find abnormal antibodies. Bone Marrow Aspiration and biopsy helps find cancerous plasma cells and imagining scans help find bone lesions. Advanced stages of myeloma is also associated with high amount of calcium in the blood

Confirmation Tests
Bone Marrow Biopsy and Aspirations
Bone Scans and/or PET/CT Scans
Liver and Kidney functioning tests
Complete Blood Count (CBC) tests
Serum Protein Tests (esp. Serum Protein Electrophoresis test)
Urine Ben Jones Protein test
Free Light Chain ratio tests
BM for cytogenetic/fluorescence in situ hybridization (FISH) studies
Key Events in Multiple Myeloma Description
Hypercalcemia >1 mg/dl higher than upper limit or >11 mg/dl
Kidney Functioning tests Serum cretinine >2mg/dl or cretinin clearance < 40ml/min
Anemia Haemoglobin less than < 10 gm/dl or >2gm/dl below the lower limit of normal
PET/CT Scan detected bone lesions Bone lesion: one or more osteolytic lesions seen in skeletal radiography, CT or PET-CT
Biomarkers
  • Clonal bone marrow plasma cells ≥ 60%
  • Free light chain ratio ≥ 100

Note: changes in these levels are used to determine staging of multiple myeloma


Treatment Options

Multiple myeloma is considered treatable, but generally incurable. Remissions may be brought about with steroids, chemotherapy, thalidomide or lenalidomide, and stem cell transplant. Bisphosphonates and radiation therapy are sometimes used to reduce pain from bone lesions.

Typically asymptomatic plasma cell disorders like MGUS and smoldering myeloma do not require treatment. They are to be kept under strict and regular follow up.

Treatment Algorithm

If a patient is having MGU's or smoldering multiple myeloma, then there is no active treatment considered typically. The patient is kept under frequent and active monitoring.

If the patient has active multiple myeloma, treatment is considered for him/her. The course of the actual treatment is decided based on each individual's current health history and discussion with a team of doctors called MDT(multi-disciplinary team).

Image on tx decision making


If the patient has active myeloma, then he/she is considered for active front line (initial) treatment. Typically the decision is driven by multiple factors and is decided by both the patient and the doctor in active discussion:

Typical Factors for front line treatment
If the patient is eligible for stem cell transplant
Current health history and patient's health status


Patients are usually given combination therapies for their front line treatment. The below image gives a basic view of the current guidelines for the treatment of multiple myeloma as well as treatment of relapse patients of multiple myeloma. These are subjected to change as per local health policies and as and when new/more effective treatments are available.


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Research and Further Readings

There are many resources on the net for reading further about cancer

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