Multiple myeloma (MM)

Multiple myeloma (hereinafter referred to as MM) is a malignant haematopoietic disease that develops as a result of the uncontrolled multiplication of monoclonal (originating from one cell) plasma cells in bone marrow. The role of plasma cells in a healthy body is to produce specific proteins responsible for non-cellular immunity. When these protein compounds are not produced sufficiently, this results in increased susceptibility to various infections.

Sick plasma cells produce a so-called paraprotein on a non-functional immunoglobulin or monoclonal protein. Haematopoiesis is impaired and surrounding bone tissue damaged. In adults, haematopoiesis takes place in flat bones (cranial bones, ribs, vertebrae, pelvic bones, etc). Multiple myeloma is a disease of the elderly, with the average age at onset being 70 years.


The most frequent disease symptom is back pain, which is caused by bone tissue damage, often even spontaneous bone fractures. In addition to the aforementioned, MM patients may develop renal failure due to the accumulation of abnormal protein or the shortage of blood cells due to the inhibition of normal haematopoiesis (including anaemia, thrombocytopenia and leukopenia).


Upon diagnosis, there are characteristic changes in the blood – a decrease in renal function, anaemia, hypercalcemia, proteinemia, a change in the immunoglobulin light chain ratio.

A specific analysis showing the presence of pathological or monoclonal protein in the blood is called proteinogram. Monoclonal protein can be determined by the electrophoretic analysis of proteins in blood serum and/or urine. This analysis makes it possible to evaluate the presence of pathological protein (M-protein, M-spike) and determine its malignancy or monoclonality, which is typical for MM.

Accumulation of monoclonal protein in the kidneys may manifest as kidney failure and massive oedemas. These patients often need haemodialysis or renal replacement therapy.

The basis of an MM diagnosis is a bone marrow investigation, which helps to determine the amount of plasma cells in haematopoiesis. During this investigation, material is taken from the bone marrow for genetic analysis (cytogenetic FISH-test) that helps to determine disease prognosis.

The extent of bone damage is evaluated using full-body computer tomography (CT). This investigation helps to determine the risk of pathological bone fractures and spinal cord compression. Mechanical pressure on the spinal cord develops when plasma cells destroy the surrounding bone tissue or vertebra and the tumorous mass compresses the nerve fibers in the spinal cord. causing severe pain, disorders of limb function and sensitivity.


Today, MM is an incurable disease. Above all, treatment is directed towards prolonging the disease-free period and maintaining quality of life.

Treatment options are quite conventional but may differ among countries due to the availability of options. Treatment choice is based on the patient’s age, prognosis, concurrent chronical diseases, general condition, presence of renal failure, etc.

Different types of medicinal products are used in treatment combinations: hormones (prednisolone, dexamethasone), chemotherapeutic agents (cyclophosphamide, doxorubicin, bendamstine), immunomodulating agents (thalidomide, lenalidomide, pomalidomide), proteasome inhibitors (bortezomib). Treatment options may individually differ due to the abovementioned factors.

Young patients (<70 years) will receive first-line intensive treatment, including transplantation of stem cells. For older patients (>70 years), intensive treatment will not be applied.

In the first-line treatment, bortezomib-based treatment regimens are used (VCD, VTD, VMP). Younger patients belonging to the intensive treatment group will receive four standard treatment courses, after which autologous (the patient’s own) stem cells will be collected and transplanted. If the treatment effect is not sufficient after four treatment courses, up to two more treatment courses will be performed before transplantation.

The cells are collected from the patient’s own blood with a special apheresis procedure. Before transplantation, myeloablative or high-dose chemotherapy is used with the aim of maximum destruction of the diseased bone marrow.
In high-risk patients, so-called tandem transplantation, i.e. two consecutive transplantations, is used to achieve the best possible treatment response.

Autologous transplantation may be considered relatively safe, but there are many complications in the post-treatment phase. During this period, infections and chronic diseases may exacerbate. Therefore, this treatment method is used only in younger and relatively more healthy patients. After this treatment method, the disease-free period lasts 1.5-3 years on an average.

Older patients will also receive bortezomib-based treatment (VMP, Vd, MPT). Treatment will be combined with hormone and/or chemotherapy. Such treatment is more sparing and the risk of treatment-related complications is smaller. The number of treatment courses may vary (8-12 treatment courses) depending on treatment response or intolerance.

For patients with a very loaded history and older patients, palliative treatment may be used with the aim of maximum maintenance of quality of life. Here, hormone preparations are used alone or in combination with chemotherapy.

Complete treatment of MM also includes so-called osteoporosis treatment (bisphosphonate treatment with zoledronic acid or pamidronic acid), which is performed regularly throughout the treatment and for two years after the treatment.

In second-line therapy, combinations based on immunomodulating agents (lenalidomide or pomalidomide) with hormone and bortezomib are indicated. Treatment will be applied until disease progression.

In third-line treatment, specific biological agent daratumumab directed against plasma cells (monoclonal antibody against CD38 surface marker) can be used. In a similar way, this medicinal product is combined with hormone and/or bortezomib. Treatment duration is unlimited; it will be done until disease progression or intolerance.

In the case of soft tissue plasma cell additional formations and bone tissue destruction and the associated pain syndrome, radiotherapy is used in addition to systemic treatment. This approach allows fast pain relief and the reduction of the compression of surrounding tissues, above all nerve tissue, caused by the tumorous mass.


Prognosis depends on the risk level of the disease (can be evaluated with genetic investigation and specific blood analyses), age and concomitant diseases. With the improvement of treatment options, survival is improving in Estonia and elsewhere in the world. In general, survival may range between 1 to 10 years, sometimes longer. Younger patients not belonging to the high-risk group have a significantly better prognosis than older patients. The prognosis of high-risk patients is poor irrespective of age. With the availability of new drugs, it is possible to prolong the disease-free period also in patients with poor prognosis.

In the case of progressing and uncontrolled disease, life-threatening complications occur due to infections, worsening of bone marrow function, worsening of renal failure as well as failure of other organs.

Compiled by: Dr Iige Viigimaa, Haematologist/Head Doctor
Last updated: 2019