Multiple myeloma

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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 solitary 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.

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, especially 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. The disease is often only recognised when other symptoms of the disease appear (symptoms of anaemia, impaired kidney function, paralysis due to vertebral fractures, other bone fractures, an increase in calcium in the blood) or when abnormal laboratory parameters are detected.

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

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

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.

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 prognosis of the disease.

It is now assumed that multiple myeloma develops in almost all cases via a precursor, monoclonal gammopathy of uncertain significance (MGUS). In MGUS, the monoclonal protein can be detected, but there are no signs of the disease. MGUS is usually detected by chance during a routine blood test. MGUS can remain inapparent for life and does not require treatment. However, as there is a risk of a transition to symptomatic multiple myeloma, regular check-ups should be carried out.

By definition, multiple myeloma is present if the number of plasma cells in the bone marrow is more than 10%. However, this does not necessarily mean that treatment must be carried out. Systemic therapy should only be started if the myeloma is symptomatic (with bone changes, anaemia, kidney dysfunction, increased calcium levels) or if certain examination parameters predict rapid progression of the disease.

A special case is solitary plasmacytoma, in which the tumour cells are only detectable at a single site. These foci can only be treated specifically with radiotherapy.

Treatment is indicated for symptoms such as bone fractures, impaired kidney function, elevated calcium or anaemia, or for asymptomatic but rapidly progressing disease with impending complications. In the past, the treatment of multiple myeloma consisted of chemotherapy (melphalan) and steroids (dexamethasone, prednisolone). In recent years, numerous new, effective drugs have been approved for multiple myeloma, which have led to an improvement in survival. These newer substances include proteasome inhibitors (such as bortezomib and carfilzomib), immunomodulatory drugs (such as thalidomide, lenalidomide and pomalidomide) and antibodies (such as daratumumab and elotuzumab), as well as new forms of immunotherapy such as bispecific antibodies (such as teclistamab) and CAR-T cell therapy. The drugs are often used in double, triple or even quadruple combinations.

The choice of drug therapy depends on various factors, such as age, general condition and concomitant diseases. The side effects of systemic therapy - such as anaemia, nausea and vomiting, hair loss or inflammation of the oral mucosa - are temporary in nature and can be alleviated or even completely prevented by medication. As a rule, multiple myeloma cannot be cured even with intensive therapy, but a long remission and control of the disease can be achieved.

High-dose chemotherapy with transfer of own (autologous) stem cells

The standard therapy for fit patients consists of so-called induction therapy followed by one or two high-dose chemotherapies with transplantation of the patient's own haematopoietic stem cells and subsequent consolidation and maintenance therapy. Induction therapy usually consists of a combination of newer substances (antibodies, proteasome inhibitors and immunomodulatory drugs) and dexamethasone. If well tolerated, this therapy can be carried out on an outpatient basis. The aim is to achieve a good response to the disease. The patient's own blood stem cells are then collected. This involves administering mild chemotherapy and growth factors so that the stem cells can be removed from the blood and frozen. This is usually carried out as an inpatient. The actual high-dose therapy can only be carried out once the patient's own stem cells have been harvested. In this process, both the myeloma cells and the healthy haematopoietic cells are largely destroyed. It takes approx. 2-3 weeks until the stem cells administered after chemotherapy have grown back and are able to produce sufficient blood. During this time, the patient requires blood transfusions and should be isolated due to their susceptibility to infection. In some patients, this procedure is carried out twice at intervals of around 3 months (so-called "double transplantation"). Following the high-dose therapy, several years of (outpatient) maintenance therapy with lenalidomide is carried out. High-dose treatment is significantly more stressful compared to less intensive therapies, but is also superior in terms of effectiveness.

Non-intensive therapy

Non-intensive therapy, either in the form of outpatient tablet or infusion 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. Nowadays, new substances (e.g. daratumumab, lenalidomide, bortezomib) are used in combination with dexamethasone and, if necessary, conventional chemotherapy. The therapy can usually be carried out completely on an outpatient basis.

Relapse

In the event of a relapse of multiple myeloma after intensive or non-intensive therapy, all of the above-mentioned drugs can be used again. Depending on how long the first therapy lasted, this can also be repeated. In the majority of cases, the myeloma is successfully regressed again.

Status: 14 July 2023