Diagnosing

Overview

Multiple myeloma is a cancer of plasma cells — the white blood cells that make antibodies. Abnormal plasma cells build up in the bone marrow, produce an abnormal protein (M-protein) and can damage bones, kidneys and the blood count.

Treatment has advanced dramatically. Although myeloma is usually not cured, many people now live well for many years with modern therapy.

Other plasma cell disorders

MGUS (monoclonal gammopathy of undetermined significance) — a small amount of M-protein without symptoms; it needs monitoring only.
Smoldering myeloma — more plasma cells or protein, but no organ damage yet.
Solitary plasmacytoma — a single tumor of plasma cells in bone or soft tissue.
AL (light-chain) amyloidosis — abnormal protein deposits that damage organs such as the heart and kidneys.
Waldenström macroglobulinemia — a related lymphoma producing IgM protein.

Causes and risk factors

Age over 60
A history of MGUS
Family history of myeloma
Obesity and certain chemical or radiation exposures

Symptoms — remember "CRAB"

Calcium raised — thirst, constipation, confusion
Renal (kidney) problems
Anemia — tiredness and breathlessness
Bone pain or fractures, often in the back or ribs
Frequent infections

Complications

Bone fractures and spinal cord compression, kidney failure, infections and blood clots. Early diagnosis and supportive care help prevent them.

Living with multiple myeloma

With treatment, bone-strengthening medicines, exercise guided by physiotherapists and regular monitoring, most patients maintain an active life.

Tests confirm myeloma, measure its activity and look for organ damage so that treatment can start at the right time.

Blood tests

Complete blood count, kidney function, calcium and albumin
Serum protein electrophoresis and immunofixation — detect and identify the M-protein
Serum free light chains — measure kappa and lambda light chains
Beta-2 microglobulin and LDH — used for staging

Urine tests

A 24-hour urine collection with electrophoresis measures light-chain protein (Bence Jones protein) passed in the urine.

Bone marrow aspiration and biopsy

Shows the percentage of abnormal plasma cells. FISH tests look for high-risk changes such as del(17p), t(4;14) and t(14;16).

Imaging tests

Whole-body low-dose CT — detects bone lesions
MRI — for the spine and pelvis, or to check for spinal cord compression
PET-CT — shows active disease and helps assess response
X-ray — of painful areas

Staging

The Revised International Staging System (R-ISS, stages I–III) combines albumin, beta-2 microglobulin, LDH and high-risk genetic changes.

Treatment

MGUS and smoldering myeloma are usually monitored. Active myeloma is treated with combinations of medicines, often followed by a transplant and maintenance therapy.

Combination drug therapy

Induction usually combines three or four medicines, for example a proteasome inhibitor (bortezomib, carfilzomib), an immunomodulatory drug (lenalidomide, pomalidomide), an anti-CD38 antibody (daratumumab, isatuximab) and dexamethasone.

Bone marrow / stem cell transplant

For eligible patients, high-dose melphalan followed by an autologous stem cell transplant deepens and prolongs the response. Lenalidomide maintenance usually follows.