Multiple myeloma: symptoms, diagnosis and modern treatment

What is multiple myeloma?

Plasma cells are white blood cells that make antibodies. In multiple myeloma, one plasma cell becomes cancerous and multiplies uncontrollably in the bone marrow. These cells produce large amounts of a single, useless antibody – the monoclonal protein (M-protein or paraprotein) – and crowd out normal blood cell production.

Myeloma belongs to the family of blood cancers, alongside leukaemia and lymphoma. It is more common in men and in people over 60–65. It is almost always preceded by a harmless-looking condition called MGUS (monoclonal gammopathy of undetermined significance), and sometimes by "smouldering" myeloma. These early stages are not treated but are monitored regularly.

Multiple myeloma symptoms

Early myeloma may cause no symptoms and is sometimes picked up by chance – for example, a raised ESR or high total protein on routine blood tests. Doctors summarise the typical features as CRAB:

• C – calcium: high blood calcium, causing thirst, passing urine often, constipation, nausea and confusion;
• R – renal: kidney damage, as the paraprotein harms the kidneys (see chronic kidney disease);
• A – anaemia: tiredness, pallor and breathlessness on exertion;
• B – bones: pain in the back, ribs or pelvis, thinning bones and fractures, including collapsed vertebrae.

Repeated infections are also common because normal antibody levels fall. Less often, people notice tingling in the hands and feet, bleeding or symptoms of thickened blood.

How myeloma is diagnosed

A diagnosis needs several tests, usually arranged by a haematologist:

• Blood tests – full blood count, creatinine, calcium, total protein and albumin, LDH and beta-2 microglobulin.
• Protein electrophoresis and immunofixation of blood and urine to detect the M-protein, plus a serum free light chain test (kappa and lambda).
• Bone marrow aspirate and biopsy – shows the percentage of abnormal plasma cells. Genetic tests (FISH) look for changes such as del(17p), t(4;14) or t(14;16), which indicate higher-risk disease.
• Imaging – whole-body low-dose CT, MRI or PET-CT to find bone lesions (see also MRI and CT scans).

The stage is set using the Revised International Staging System (R-ISS), which combines albumin, beta-2 microglobulin, LDH and high-risk genetic changes.

When does treatment start?

Not everyone with a paraprotein needs treatment. Therapy starts for active (symptomatic) myeloma – when CRAB features are present or when certain "myeloma-defining" markers are found, such as more than 60% plasma cells in the marrow, a very high free light chain ratio, or more than one lesion on MRI. MGUS and low-risk smouldering myeloma are usually just monitored. The decision always rests with a haematologist.

Modern treatment of multiple myeloma

Treatment is given in phases, usually combining three or four medicines from several classes:

• proteasome inhibitors and immunomodulatory drugs;
• monoclonal antibodies against the CD38 protein on myeloma cells;
• corticosteroids, given alongside the above.

Autologous stem cell transplant. For suitable patients – generally up to around 70 and in good overall health – a few cycles of initial treatment are followed by collection of the patient's own stem cells, high-dose chemotherapy and return of the stem cells. Maintenance treatment, usually with an immunomodulatory drug, follows.

At relapse, effective newer options exist: bispecific antibodies that redirect the patient's own T-cells against myeloma, and CAR-T cell therapy targeting the BCMA protein. These are given in specialist centres.

The goal is a deep response – ideally minimal residual disease (MRD) negativity, which is linked with longer remissions.

Supportive care

Supportive treatment is an essential part of living well with myeloma:

• bone-strengthening medicines (bisphosphonates or an anti-RANKL antibody) reduce fractures; a dental check is advised before starting;
• radiotherapy or surgery for painful lesions or bones at risk of breaking, and vertebroplasty for collapsed vertebrae;
• vaccinations and infection prevention, sometimes with immunoglobulin replacement;
• drinking enough fluid and avoiding anti-inflammatory painkillers to protect the kidneys;
• blood clot prevention with some treatments;
• managing pain and nerve damage, staying active, good nutrition and emotional support.

Follow-up and living with myeloma

Once the myeloma has responded, people are monitored regularly – usually every one to three months – with blood tests for the paraprotein and free light chains, a blood count, kidney function and calcium. Scans are repeated if new symptoms appear or when the haematologist considers them necessary. A rising paraprotein can come months before any symptoms, so it is important not to skip check-ups.

Many people with myeloma keep working, travel and lead active lives. Regular exercise suited to the state of your bones, not smoking and prompt treatment of infections all help. In advanced disease, palliative care helps with pain control and supports the family, alongside active treatment.

When to see a doctor

See your GP if you have ongoing back or bone pain with no clear cause, unexplained tiredness, frequent infections, or if blood tests have shown anaemia, high protein, high calcium or reduced kidney function. They can refer you to a haematologist. If you know you have MGUS, keep to your follow-up tests.

Seek emergency help (call 112) for sudden severe back pain with weakness or numbness in the legs or loss of bladder or bowel control – this may mean pressure on the spinal cord. A high temperature during treatment, marked confusion or a sharp fall in urine output are also emergencies.

Myeloma treatment abroad and in Türkiye

Some patients from Bulgaria and elsewhere in Europe seek a second opinion or treatment at large accredited hospital groups in Istanbul with haematology departments, stem cell transplant units and access to cellular therapies. Because myeloma treatment is long, agree at the outset which phases will take place there and how maintenance and monitoring will continue at home. Ask for a written plan and check the experience of the haematologist and the centre. Organisers such as New City Clinic coordinate the hospital, doctor, hotel, transfers and interpreter, while medical decisions remain with the treating team. For the broader picture, see modern cancer treatment.