Myeloma is a type of cancer affecting the plasma cells in the bone marrow. Plasma cells are B lymphocytes that produce antibodies. Cancer in a specific type of plasma cell results in the production of large quantities of a specific paraprotein (or M protein), which is an abnormal antibody or part of an antibody.

Multiple myeloma is where the myeloma affects multiple bone marrow areas in the body.

Monoclonal gammopathy of undetermined significance (MGUS) involves the production of a specific paraprotein without other features of myeloma or cancer. Monoclonal refers to identical copies or clones originating from a single cell. MGUS is often an incidental finding in an otherwise healthy person. It has a small risk of progression to myeloma (about 1% per year).

Smouldering myeloma involves abnormal plasma cells and paraproteins but no organ damage or symptoms. It has a greater risk of progression to myeloma (about 10% per year).



Plasma cells are B lymphocytes of the immune system that have developed to produce a specific antibody. Antibodies are also called immunoglobulins. They are complex molecules made up of heavy chains and light chains arranged in a Y shape. They help the immune system recognise and fight infections by targeting specific proteins on the pathogen. The five types of antibodies are A, G, M, D and E. 

Myeloma is cancer of a single type of plasma cell, with a genetic mutation that causes them to rapidly and uncontrollably multiply. They produce a specific paraprotein (or M protein), which is an abnormal antibody (immunoglobulin) or part of an antibody (often the light chain). There is an abnormally high level of this paraprotein (paraproteinaemia).

The Bence Jones protein refers to free light chains in the urine. 


Four Features

The CRAB mnemonic can be used to remember the four key features of myeloma:

  • CCalcium (elevated)
  • RRenal failure
  • AAnaemia
  • BBone lesions and bone pain



Anaemia is the most common complication of myeloma. The cancerous plasma cells invade the bone marrow (bone marrow infiltration), resulting in suppression of the other blood cell lines, leading to anaemia (low haemoglobin), leukopenia (low white blood cells) and thrombocytopenia (low platelets). Anaemia in myeloma is normocytic (normal size) and normochromic (normal colour). 


Myeloma Bone Disease

Myeloma bone disease results from increased osteoclast activity and suppressed osteoblast activity. Osteoclasts absorb bone, and osteoblasts deposit bone. The metabolism of bone becomes imbalanced, with more bone being reabsorbed than constructed. It is caused by cytokines released from abnormal plasma cells and other nearby cells.

Common sites of myeloma bone disease are the skull, spine, long bones and ribs. The abnormal bone metabolism is patchy, meaning that the bone becomes very thin in some areas while others remain relatively normal. These patches of thin bone are described as osteolytic lesions. These weak points in the bone lead to pathological fractures. For example, a vertebral body in the spine may collapse (vertebral fracture), or a long bone such as the femur may break under minimal force.

Increased osteoclast activity causes calcium reabsorption from the bone into the blood, resulting in hypercalcaemia.

Plasmacytomas are individual tumours formed by cancerous plasma cells. They can occur in the bones, replacing normal bone tissue, or in the soft tissues.


Renal Disease

Patients with myeloma often develop renal impairment, which can have various causes:

  • Paraproteins deposited in the kidneys
  • Hypercalcaemia affecting kidney function
  • Dehydration
  • Glomerulonephritis (inflammation around the glomerulus and nephron)
  • Medications used to treat the condition


Hyperviscosity Syndrome

The normal plasma viscosity, or internal friction in blood flow, is between 1.3 and 1.7 times that of water. An oversimplified description is that blood is 1.3 to 1.7 times thicker than water. Plasma viscosity increases when more proteins are in the blood, such as the paraproteins found in myeloma.

Hyperviscosity syndrome is considered an emergency. It can cause many issues:

  • Bleeding (e.g., nosebleeds and bleeding gums)
  • Visual symptoms and eye changes (e.g., retinal haemorrhages)
  • Neurological complications (e.g., stroke)
  • Heart failure


Risk Factors

  • Older age
  • Male
  • Black ethnic origin
  • Family history
  • Obesity



The presenting features that should raise suspicion of myeloma include:

  • Persistent bone pain (e.g., spinal pain)
  • Pathological fractures
  • Unexplained fatigue
  • Unexplained weight loss
  • Fever of unknown origin
  • Hypercalcaemia
  • Anaemia
  • Renal impairment



The information below is simplified from the NICE CKS (updated 2022) and guidelines (updated 2018) on myeloma.

Laboratory investigations include:

  • FBC (anaemia or leukopenia in myeloma)
  • Calcium (raised in myeloma)
  • ESR (increased in myeloma)
  • Plasma viscosity (increased in myeloma)
  • U&E (for renal impairment)
  • Serum protein electrophoresis (to detect paraproteinaemia)
  • Serum-free light-chain assay (to detect abnormally abundant light chains)
  • Urine protein electrophoresis (to detect the Bence-Jones protein)


Bone marrow biopsy is required to confirm the diagnosis and perform cytogenetic testing.

Imaging is used to assess for bone lesions. The order of preference is:

  1. Whole-body MRI
  2. Whole-body low-dose CT
  3. Skeletal survey (x-ray images of the entire skeleton)


X-ray Findings

Typical x-ray changes seen in patients with myeloma include:

  • Well-defined lytic lesions (described as looking “punched-out”)
  • Diffuse osteopenia
  • Abnormal fractures


Raindrop skull (sometimes called pepper pot skull) refers to multiple lytic lesions seen in the skull on an x-ray. 



An oncology and haematology multi-disciplinary team will coordinate treatment. Treatment aims to control the disease. It takes a relapsing-remitting course and is never fully cured.

Treatment usually involves a combination of chemotherapy, which may include:

  • Bortezomib (a proteasome inhibitor)
  • Thalidomide
  • Dexamethasone


High-dose chemotherapy followed by a stem cell transplant is an option for fitter patients and may achieve a more extended period of remission. Stem cell transplantation can be:

  • Autologous (using the person’s own stem cells)
  • Allogeneic (using stem cells from a healthy donor)


Management of myeloma bone disease may involve:

  • Bisphosphonates to suppress osteoclast activity
  • Radiotherapy for bone lesions can improve bone pain
  • Orthopaedic surgery to stabilise bones (e.g., by inserting a prophylactic intramedullary rod) or treat fractures
  • Cement augmentation (injecting cement into vertebral fractures or lesions) to improve spine stability and pain



There are many complications of myeloma and its treatment, including:

  • Infection 
  • Bone pain
  • Fractures
  • Renal failure
  • Anaemia
  • Hypercalcaemia
  • Peripheral neuropathy
  • Spinal cord compression
  • Hyperviscosity syndrome
  • Venous thromboembolism


Last updated August 2023