Are lesions caused by multiple myeloma curable

What is multiple myeloma (plasmacytoma)

Multiple myeloma is a malignant disease of the plasma cells in the bone marrow. Myeloma cells can also grow in the form of circumscribed "tumors" called plasmacytomas. Such plasmacytomas can either be in the bone marrow or bone (intramedullary) or develop outside the bone, in the soft tissue (extramedullary). In the case of malignant diseases, one usually looks for metastases. Multiple myeloma is about changes in the bone marrow.

In multiple myeloma, a malignant type of plasma cell multiplies (hence the expression: monoclonal = starting from a single strain). As a result, only one kind of repellent is produced in oversized quantities, which also does not work properly. The healthy plasma cells are suppressed. As a result, however, the other defenses are also produced in insufficient quantities. If the pathogenic defensive white is found in large quantities, we speak of a paraprotein, also called M-protein.

Plasma cells belong to the group of white blood cells, also called leukocytes. In our body, the various leukocytes work together to defend against infections. Within this defense system, the plasma cells are responsible for the production of defense proteins, the immunoglobulins. In the event of an infection, various plasma cells grow to produce defensive proteins (antibodies) and thus strengthen the immune system.

The clinical picture in myeloma is characterized by the increasing accumulation of myeloma cells in the bone marrow, which can result in the following symptoms:

  • Impairment of normal blood production in the bone marrow, which leads to anemia and / or a decrease in the number of leukocytes or platelets in the blood.
  • Damage to the surrounding bone.
  • Secretion of a monoclonal protein (M-protein) by the myeloma cells, which can be detected in the blood and / or in the urine and which can lead to a wide range of symptoms.
  • Impairment of the functional immune system with a decrease in normal immunoglobulins and an increased susceptibility to infections. Infections also occur more frequently when the number of white blood cells in the blood is low.

More rarely, the protein chains are not completely produced, but only a fragment (so-called Bence Jones protein) is formed: light chain myeloma. Even rarer is the form in which the plasma cell proliferates but no longer produces defensive white cells: non-secreting myeloma.

In some cases, myeloma cells multiply very slowly in the bone marrow. The earliest stage of plasma cell disease is so-called monoclonal gammopathy of indefinite significance (MGUS). In MGUS, there is less than 10% infiltration of plasma cells in the bone marrow. There is a risk of developing myeloma, but this is very low and is around 1% per year. Even with bone marrow infiltration of 10-30%, the growth rate can be very low, in which case one speaks of smoldering or asymptomatic myeloma. In these cases, changes occur very slowly, and treatment is often unnecessary for years.


In order to be able to make a diagnosis of multiple myeloma, various conditions must be met. The reason is that a paraprotein can be found in many elderly people without plasma cells proliferating: benign paraproteinemia. There are also other diseases in which the number of plasma cells in the bone marrow can be increased for the purpose of natural defense.

The criteria of the World Health Organization (WHO) are used for diagnosis.
The following values ​​are included:

  • the level of the protein content
  • Number of foci in the bones
  • the number of plasma cells in the bone marrow
  • the presence of Bence Jones protein in the urine
  • low levels of normal defenses.

So far, multiple myeloma has been divided into three stages according to the classification of Salmon and Durie (see table); depending on the level of paraprotein, (non) anemia and / or lack of platelets, the level of calcium in the blood and the extent to which bones are damaged. A division into A (well-functioning) and B (poorly-functioning) is made depending on the kidney function.

criteriaall the following criteria:
  • Hemoglobin> 100 g / l
  • Serum calcium normal
  • Radiographically examined normal bone structure or just a solitary focus
  • low serum myeloma protein concentration
  • at IgG <50g / l
  • with IgA <30g / l
  • Bence Jones in urine <4g / 24h
neither stage I nor stage IIIa or several of the following criteria:
  • Hemoglobin <85 g / l
  • Serum calcium increased
  • advanced bone lesions
  • high serum myeloma protein concentration
  • at IgG> 70g / l
  • at IgA> 50g / l
  • Bence Jones in the urine> 12g / 24h
Tumor cell mass<0.6 x 1012/ m2 Body surface> 0.6 x 1012/ m2 Body surface> 1.2 x 1012/ m2 Body surface
Kidney functionSerum creatinine <2mg / dl: stage A.Serum creatinine <2mg / dl: stage B.

The classification says something about the severity of the disease and the prognosis. In stage IA, therapy can still be dispensed with. Treatment is not necessary at this stage and waiting for the situation to get worse will not do any harm. The drugs are saved for the time when they are really needed and the patient is not burdened with side effects of the treatment at an early stage.

With the international staging system ISS (International Staging System) the introduction of a new, updated classification is currently being examined. This system is based on data from over 10,000 myeloma patients. Predictive factors such as the ß2-microglobulin value play an important role in the new classification. (β2-microglobulin works like a tumor marker, i.e. it reflects the tumor mass and aggressiveness and the serum albumin is a protein that reflects the nutritional and general condition, i.e. how sick the patient is).

International Staging System (ISS) (according to

Stage I.ß2-microglobulin value <3.5
Albumin> 3.5
Stage IIß2-microglobulin value <3.5
Albumin <3.5 or ß2-microglobulin 3.5 - 5.5
Stage IIIß2-microglobulin value> 5.5

Serum-ß2-microglobulin in mg / l - serum albumin in g / dl

In addition, a system has been developed with which the doctor can make a therapy selection in order to help the patient effectively. This system - also called "CRAB" - is based on the following criteria:
(C) (Calcium elevation) Increase in calcium levels
(R) (Renal insufficiency) kidney failure
(A) (anemia) anemia, (too few red blood cells)
(B) (Bone abnormalities) Changes in the bones

The International Myeloma Working Group (IMWG) updated and expanded the CRAB criteria in 2014. The so-called SLiM criteria, sometimes also referred to as "biomarkers", have been added - especially for patients who are still symptom-free:

(S) (English sixty = 60), more than 60% clonal plasma cells in the bone marrow, i.e. in the bone
(Li) (Light chain = light chains), in the serum the ratio of the involved to the uninvolved free light chains is 100 or more.
(M) (MRI) Whole-body magnetic resonance imaging reveals more than one bone damage that is at least 5 mm in size.

Treatment should be initiated if one of these SLiM criteria is met, regardless of whether any of the CRAB criteria are met.

The slim criteria reflect the following:
≥ 60% clonal plasma cells, i.e. there is a lot of myeloma in the bone marrow.
≥ 100 light chain ratio, this occurs when the diseased light chains are greatly increased at the same time as the healthy but also reduced, i.e. the diseased cells have displaced the healthy plasma cells.
MRI lesions reflect incipient bone involvement that is not yet as pronounced as it would have been visible in the X-ray (= B in CARB = bone leson).

In summary: A patient who does not meet the CRAB criteria has a disease that progresses smoothly. But this is not always the case. There are also differences among the less aggressive myeloma diseases. The Slim criteria help to distinguish between a calm disease or a severe disease, but still at an early stage.

Risk factors

So far, no single factor has been identified that is unequivocally associated with the development of multiple myeloma. However, exposure to certain chemicals (e.g. chemicals used in agriculture) has been found to increase the risk of myeloma and related diseases. Viruses have also been discussed as triggering factors, such as the human immunodeficiency virus (HIV), hepatitis viruses, the human herpes virus 8 (HHV-8) and others.

Case-controlled studies from the USA clearly show an increased risk for family members of those affected. Siblings of myeloma sufferers were found to be about four times more likely to develop myeloma within 10 years.

Myeloma is a disease of old age

The average age of patients at diagnosis is between 60 and 65 years. Only 5-10% of patients are under 40 years of age. The condition is more common in men than women and is also found to be more common in certain ethnic groups, such as African-Americans.

The main problems

The main problems with multiple myeloma are:

The growth of plasma cells in the bone marrow can attack the bones. The consequences are bone pain and even spontaneous fractures. In this context, problems in the vertebrae, which often collapse, are notorious. The attacks on the bones can also lead to an increase in the calcium content in the blood (hypercalcemia).
The displacement of healthy bone marrow cells by cancer cells can hinder the production of normal red blood cells and thus lead to anemia (anemia). A platelet deficit can also arise, which increases the risk of bleeding. The impaired production of white blood cells (leukocytes) leads to a disruption in the immune system. Therefore, the risk of infection is increased. The patient will also recover less quickly as a result.
The risk of infection is not only increased because of the insufficient number of immune cells, but also because of the lack of normal defense cells. The cancer cells only produce one kind of defensive protein, all others are only produced in insufficient numbers.
Some myeloma patients have disorders of kidney function. These are caused, among other things, by the precipitation of Bence Jones protein, by dehydration when the calcium content is too high and the blood uric acid content is high. There are often combinations of these factors that explain poor kidney function.


Until the first cytostatics (cell-killing drugs) hit the market, the prognosis was extremely poor. Treatment methods have been extensively researched in recent years, and today, with fairly mild therapy, significant improvement can be achieved. However, the disease is still not curable. The mean life expectancy from the moment of diagnosis is between 4 and 6 years. This is a statistical mean that says that 50% of the patients are still alive at this point in time. How long these will still live is not said with that. There are patients whose diagnosis was 10, 15 or even 20 years ago.

In order to increase life expectancy, more intensive treatment is now used, especially in younger patients. In particular, the importance of autologous (= from the patient) and allogeneic (= from a suitable third-party donor) stem cell transplantation has been intensively investigated in recent years. Life expectancy seems to be increasing, but the chance of a cure is still slim. Only a small group of younger patients can receive such strong therapy.

The new drugs that have been on the market for several years or are about to be launched have significantly improved the prognosis. This emerges from a recently published study which shows longer survival in patients who have been treated during the last few years compared to patients from the early 1990s.

In recent years, disease-related factors have also emerged as important prognostic indicators. Changes in the structure and composition of the chromosomes (carriers of the genetic material) in the myeloma cells allow a prediction of therapy response and survival time.

The lack of chromosome 17 or a mutual exchange of fragments of chromosomes 4 and 14, for example, have a particularly unfavorable effect. Other changes, such as additional chromosomes, are associated with a more favorable prognosis.
The sole deletion (loss) of chromosome 13 does not represent a risk. In numerous cases, the deletion of chromosome 13 occurs together with other, unfavorable chromosonal anomalies.

The medical contributions were made by Prof. Dr. Jakob Passweg, Chief Physician and Head of Hematology at the University Hospital Basel, revised and updated in May 2016 based on the latest findings.