Multiple Myeloma

What is Multiple Myeloma?

Multiple Myeloma, also known as Kahler’s disease, is a cancer of the antibody-producing white blood cells known as plasma cells. In this, the abnormal plasma cells grow in large numbers in the bone marrow and result in reduced production of antibodies to fight infections, as well as reduced production of other healthy blood cells.

Alternate names

• Myeloma
• Myelomatosis
• Plasma Cell Myeloma

Is Multiple Myeloma condition a Medical emergency?

Multiple Myeloma is not a medical emergency, but early diagnosis and management are advisable to prevent complications.

Causes

The exact cause of Multiple Myeloma is not fully understood. A number of factors such as the noncancerous monoclonal gammopathy of undetermined significance (MGUS), genetic predisposition, and environmental factors can all play a role in the abnormal development and multiplication of the plasma cells within the bone marrow. Some known factors that play a role in the development of Multiple Myeloma include:

• Monoclonal Gammopathy of Undetermined Significance (MGUS)
• Genetic predisposition
• Exposure to chemicals, benzene and solvents, pesticides, herbicides
• Exposure to radiation
• Infection with Human Herpesvirus 8

Risk factors

Factors that increase the risk of Multiple Myeloma include:

• Age – more common after the age of 60 years
• Gender – more common in men
• Race – more common in Africans and African Americans
• Family history of Multiple Myeloma
• History of MGUS

Symptoms & signs

The signs and symptoms of Multiple Myeloma vary greatly between individuals and the organ system involved and may include:

• Bone pain
• Pathological fractures
• Fatigue
• Bleeding
• Anemia
• Dizziness
• Shortness of breath
• Recurrent infections
• Weight loss
• Nausea
• Loss of appetite
• Constipation
• Excessive thirst
• Confusion
• Headaches
• Vision disturbances
• Loss of bowel or bladder control
• Numbness or loss of sensation in the legs
• Enlargement of the liver

Investigations

Some investigations that may be advised for the evaluation of Multiple Myeloma may include:

• Laboratory tests:
  • CBP & ESR
  • C-Reactive protein
  • Complete metabolic panel
  • Liver function tests
  • Renal function tests with BUN, creatinine, and uric acid
  • Complete urine analysis with 24-hour urine collection for quantification of Bence Jones Proteins
  • Serum Protein Electrophoresis (SPEP)
  • Quantitative Immunoglobulin levels
  • Beta2 microglobulin levels
  • Serum viscosity levels – if there is evidence of central nervous system involvement
  • Cytogenetic analysis
• Imaging tests:
  • X-rays of the skull, spine, long bones, and chest
  • MRI scan – spine
  • PET scan
  • Bone scan
• Bone marrow aspiration and Biopsy

Diagnosis

A diagnosis of Multiple Myeloma is established based on medical history, clinical evaluation, and results of the investigations done.

Course & stages

Multiple Myeloma is staged as follows:

• Stage I: Beta-2 microglobulin ≤3.5 g/dL and albumin ≥3.5 g/dL, CRP ≥4.0 mg/dL, Plasma cell labeling index < 1%, Absence of chromosome 13 deletion, Low serum IL-6 receptor, Long duration of the initial plateau phase, Serum lactate dehydrogenase levels at or below the upper limit of normal, and standard risk chromosomal abnormalities on fluorescence studies
• Stage II: The parameters are in-between stage I & III
• Stage III: Beta-2 microglobulin levels of >5.5g/dl, high-risk chromosomal abnormalities on fluorescence studies, and serum Lactate Dehydrogenase levels more than the upper limit of normal

Treatment options

There is no cure for Multiple Myeloma. The aim of treatment is to slow the progress of the disease and prevent complications. Asymptomatic Multiple Myelomas (Smoldering Multiple Myeloma) do not require any treatment and are monitored with watchful waiting. Symptomatic Multiple Myeloma may be managed with medical or interventional management.

Medical management

Medical management of Multiple Myeloma may include:

• Chemotherapy
• Immunotherapy with immunomodulators such as Interferon Alpha 2B
• Targeted cell therapy with monoclonal antibodies
• Immunosuppressant agents such as thalidomide – used in combination with corticosteroids
• Corticosteroids
• Selective Inhibitors of nuclear export such as Selinexor
• Analgesics and Pain-relieving medications
• Biphosphonates – to help with bone-building
• Anti-BCMA antibodies – has antitumor activity against Multiple Myeloma tumor cells
• Colony-stimulating factors – for production of healthy blood cells

Interventional including surgery and indications for surgery

Interventions for the management of Multiple Myeloma may include:

• Bone marrow transplantation
• Management of and fixing of fractures
• Surgical decompression of the spine

Radiation

Multiple Myeloma is highly sensitive to radiation, but it also results in early bone loss and inflammation, it is therefore selectively used.

Role of diet/ Exercise/ Lifestyle changes/ Preventive measures

Some measures that are needed for the management of Kahler’s disease include:

• Calcium supplementation if there are low calcium levels and the individual is on bisphosphonate therapy
• Maintaining an active lifestyle
• Eating a healthy and nutritious diet
• Use of mobility aids if there is severe bone pain in the lower extremities

Complications

Some complications associated with Multiple Myeloma include:

• Pathological fractures
• Recurrent infections
• Spinal cord compression
• Severe anemia
• Renal failure
• Amyloidosis
• Death

Prognosis

The prognosis for Kahler’s disease depends on tumor mass and the rate at which the abnormal cells multiply. The prognosis tends to be poor in individuals with high tumor mass, high calcium levels, high levels of Bence Jones proteins, and renal failure. The overall survival is between 3-5 years with treatment.

When to contact the doctor or hospital? / How to identify the emergency or complications?

It is advisable to seek medical attention if the signs and symptoms of Multiple Myeloma are present.

Indications for hospitalization if required

Hospitalization is not required for the management of Multiple Myeloma unless surgical interventions are advised.

Suggested clinical specialist/ Departments to consult for this condition

• Hematology
• Oncology