The term "multiple myeloma" (MM) refers to a malignant disease of the bone marrow. As with other tumour diseases, the disease is usually caused by the degeneration of a single cell. The cell of origin of MM is the plasma cell. Plasma cells belong to the white blood cells and are found in the bone marrow, but also in other body tissues. Their task is to produce antibodies (also known as immunoglobulins). Antibodies play an important role in the human immune system by helping to defend against viruses, bacteria and other infectious agents.

MM accounts for around 1% of all malignant diseases in humans. Compared to other tumour diseases (breast cancer, bowel cancer, lung cancer), MM is therefore a rare disease. In Europe, around 4 out of every 100,000 people are diagnosed with MM each year. MM is typically a disease of older people. The average age of onset is 71 years. The name of the disease is based on the heart-shaped growth of tumour cells in many areas of the bone marrow. If only one centre of the disease can be detected in a patient, it is referred to as a solitary plasmacytoma. The distinction between plasmacytoma and MM makes sense in view of the different treatment of these two plasma cell diseases. In German-speaking countries, the two terms are also used interchangeably by doctors. Although tumour cells may also be detectable in the bloodstream in advanced forms of the disease, myeloma is not a form of leukaemia. The disease is formally categorised as a lymphoma (cancer of the lymph glands), although lymph glands (lymph nodes) are rarely affected.

The causes of the disease are largely unknown. Strong ionising radiation (radioactive), congenital immunodeficiencies and certain autoimmune diseases can apparently increase the risk of developing multiple myeloma. It is very rare for the disease to run in families, but it is not considered a hereditary disease. Unlike other cancers (e.g. lung cancer caused by smoking), there is no known risk behaviour that favours myeloma. Consequently, there are no preventive measures for malignant plasma cell diseases that could prevent the disease.

Multiple myeloma can exist for several years without any signs of the disease. Symptoms often only occur at an advanced stage. In the majority of patients, MM is characterised by bone pain, particularly back pain. Although many people complain of back pain, this is only very rarely caused by a malignant disease involving the bone, which is why "signs of wear and tear" (degenerative changes) in the musculoskeletal system are often initially blamed for the patient's pain. For this reason, weeks to months often pass between the onset of bone pain and the diagnosis of myeloma. In many patients, pain therapy (tablet therapy, "injection treatment") is initially initiated or attempts are made to provide relief through physical measures (massages, "dislocation"). The disease is often only recognised when other symptoms of the disease occur (complaints of anaemia, impaired kidney function, paralysis due to vertebral fractures, an increase in calcium in the blood) or when abnormal laboratory parameters are detected.

In addition to bone pain, other possible symptoms of myeloma disease include

• Signs of anaemia, such as fatigue, lack of drive, shortness of breath on exertion or headaches
• Susceptibility to infections with frequently recurring, persistent infections
• Signs of impaired kidney function, such as weight gain due to fluid retention in body tissue (oedema)
• Signs of an increase in calcium in the blood (hypercalcaemia)

There are also patients who are diagnosed with the disease by chance, e.g. after abnormal laboratory values are detected during a routine blood test.

If you are suspected of having multiple myeloma, various examinations are necessary: physical examination, laboratory tests (blood and urine), bone imaging (e.g. computer tomography), bone marrow puncture. Under certain circumstances, further instrumental examinations (e.g. magnetic resonance imaging) may be necessary.

Medical history, physical examination, laboratory tests

During a detailed consultation, you will tell the doctor about your symptoms and previous illnesses. This is followed by a physical examination and a series of blood and urine tests.

Imaging

X-rays, usually in the form of computer tomography (CT), are taken of almost all bones in order to detect bone changes such as circumscribed dissolution zones (so-called osteolyses), bone fractures or generalised reduction of bone substance (as in osteoporosis). Nowadays, magnetic resonance imaging is also often carried out, and in certain cases a so-called PET-CT scan is also used.

Bone marrow puncture

It is always necessary to obtain bone marrow by puncturing the pelvic bone under local anaesthetic in order to microscopically confirm the presence of degenerated plasma cells in the bone marrow.

The stage of the disease (Salmon/Durie stage) is determined for all patients with multiple myeloma. Most patients have stage III (highest stage) of the disease at the time of diagnosis. The Salmon and Durie staging system, which was defined in 1975, has become less important in recent years, as there are now more reliable characteristics for estimating the course of the disease.

Today, the following distinctions are more decisive for the clinical care of patients than the pure staging: precursor not requiring treatment (MGUS) or malignant plasma cell disease (plasmacytoma/MM); localised (plasmacytoma) or generalised (MM) disease; symptomatic MM or asymptomatic MM. asymptomatic MM.
These distinctions result in treatment decisions: no treatment (MGUS); radiotherapy (plasmocytoma); chemotherapy (symptomatic MM or asymptomatic myeloma with risk factors present); follow-up (asymptomatic myeloma).

The standard procedures for the treatment of multiple myeloma include systemic drug therapy, including chemotherapy, stem cell transplantation and new substances, radiotherapy and a combination of these procedures.

Chemotherapy

Treatment is started if the disease is symptomatic (e.g. pain due to bone changes) or asymptomatic but rapidly progressing, or if there is a risk of complications. The choice of chemotherapy depends on various factors, such as age, general condition and concomitant diseases. The side effects of chemotherapy - such as anaemia, nausea and vomiting, hair loss, inflammation of the oral mucosa - are temporary in nature and can be alleviated or even completely prevented by medication.

• Normal-dose (conventional) chemotherapy
  Conventional chemotherapy, usually in the form of outpatient tablet therapy, is indicated for patients who are not eligible for more intensive forms of therapy due to their age or concomitant illnesses, or who refuse high-dose therapy after being fully informed of the burdens and risks.
• High-dose chemotherapy, transfer of own (autologous) stem cells
  High-dose chemotherapy with transplantation of the patient's own stem cells is now the standard therapy for most patients up to the age of around 70. This procedure is often carried out twice at intervals of around 3 months (so-called "tandem transplantation"). High-dose treatment is more stressful than chemotherapy in conventional doses (then without stem cell replacement), but is also superior in terms of effectiveness.
• New substances
  The treatment options for MM have developed significantly in recent years. In particular, the use of the immunomodulating substances thalidomide, lenalidomide and pomalidomide, the proteasome inhibitors bortezomib, carfilzomib and ixazomib and the monoclonal antibodies (daratumumab, isatuximab and elotuzumab) have significantly improved response rates and survival compared to the previous standard therapies. Combinations of these drugs are now used as standard therapy both in first-line therapy for patients who do not qualify for high-dose therapy and in "induction therapy" prior to high-dose therapy. By combining several of these substances at the start of treatment, response rates have been significantly increased. In addition, new forms of immunotherapy such as the antibody-drug conjugate belantamab mafodotin or Car-T cells (the patient's own genetically modified immune cells) can be used in pre-treated patients. Several bispecific antibodies are also undergoing clinical trials.

Radiotherapy

Radiotherapy is used to relieve bone pain and stabilise bones at risk of fracture. The therapy is usually carried out on an outpatient basis in several sessions.

Bone stabilising therapy

Bisphosphonates and denosumab are used to relieve bone pain, stabilise bones and prevent fractures. Bisphosphonates are usually administered in the form of monthly infusions, while denosumab is injected subcutaneously (under the skin).

The frequency of follow-up examinations depends on the type of previous treatment and the activity of the disease. As a rule, they should be carried out at intervals of around 3-6 months. An outpatient or inpatient rehabilitation programme is particularly useful after intensive treatment measures (e.g. high-dose chemotherapy).

It makes sense for the doctor and patient to discuss and define the goals of treatment together. In the sense of an open doctor-patient relationship, realistic goals must be set. For older patients in particular, it is not a realistic goal to cure the disease completely. Especially at the beginning of the disease, most patients have completely different goals in the foreground anyway, e.g. achieving freedom from pain, maintaining kidney function or overcoming a threatening infection. Some of these goals can initially be achieved relatively quickly without chemotherapy (e.g. freedom from pain through consistent, intensive pain therapy or treatment of an infection with antibiotics), but in the case of "symptomatic" myeloma, cytostatic (tumour cell-killing) therapy is usually necessary. Thanks to the wide range of treatment options available today, the disease can be well controlled for many years in most patients.

The course of the disease is very variable. The prognosis of patients with MM has improved considerably in recent years. However, a cure for multiple myeloma is still only possible for a minority of patients. For most patients, the aim of treatment is therefore to prolong their lives while maximising their quality of life.