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Multiple myeloma

The information provided on www.fcarreras.org pretend to support, not replace, the relationship between patients/visitors of this website and their doctor.

Dr. Albert Oriol. Member of the Catalan Institute of Oncology Hematology Service, Badalona. Researcher at the Josep Carreras Leukaemia Research Institute

What is multiple myeloma?

Multiple myeloma (MM) is a cancer of a type of bone marrow cell called plasma cells. Normal plasma cells form part of the immune, or body's defence, system and are responsible for producing immunoglobulins, proteins that are capable of attacking germs when faced with infection. Under normal conditions, and throughout their entire existence, mature plasma cells produce a single type of immunoglobulin and do not reproduce.

Certain genetic alterations can enable plasma cells to recover the ability to reproduce themselves and to partially occupy the bone marrow. This situation does not always produce a clinical disorder and if the process is asymptomatic it is referred to as a monoclonal gammopathy of undetermined significance, or quiescent myeloma (QM). People in whom MGUS or QM is detected do not require treatment, but they do need to be monitored regularly given the risk that they may develop an active MM.

A clinically active MM interferes with the normal functioning of the bone marrow, causing anemia (decrease in the number of red blood cells) and an increased risk of infection, since it interferes with the normal functioning of the immune system. It also interferes with the mechanisms of bone remodelling and causes calcium deficiency (lytic, or bone lesion) which usually causes intense bone pain, increases the risk of spontaneous fracture and is associated with increased levels of calcium in the blood (hypercalcemia) which can also cause serious alterations. Bone pain is one of the main symptoms of myeloma. As with normal plasma cells, MM cells produce an immunoglobulin, called a monoclonal band or monoclonal component. This immunoglobulin can accumulate in the kidney and cause kidney problems.

When multiple myeloma causes one of these alterations, anemia, hypercalcemia, bone lesion or kidney problems, it is said to be causing 'target organ' damage and it is necessary to start treatment as soon as possible. On the other hand, when the myeloma is asymptomatic, it does not require immediate treatment because the myeloma may remain asymptomatic for years, or throughout life. Nevertheless, there are certain markers (observable in blood tests, bone marrow analysis, or imaging studies) that predict that symptoms will soon appear and these too are considered criteria for starting treatment early.

Whom does multiple myeloma affect and what causes it?

In Europe, there are approximately 40 new cases of MM per million, per year. It characteristically affects older people, more than half of patients are diagnosed after the age of 65 or 70. The disease can, however, also affect young adults.

There is no known direct cause for the appearance of multiple myeloma. Factors that increase the risk of other neoplasms such as radiation, viruses, tobacco and alcohol do not seem to bear any relation to the disease. The plasma cell precursors undergo programmed genetic alterations in the lymph nodes during their process of 'specialisation'. Errors in these genetic changes are possibly what causes the development of families of anomalous plasma cells which later become installed in the bone marrow. So far, no virus or toxic element has been identified that facilitates these erroneous genetic mutations, and neither is it known why, in some people, these alterations lead only to the development of MGUS that never progresses to a myeloma, while in others, the progression from MGUS to MM is very rapid.

What are the symptoms of multiple myeloma and how is it diagnosed?

The frequency with which routine blood tests are presently conducted means that it is ever more usual to diagnose MM by chance when it is still asymptomatic.

The most frequent symptom of MM is bone pain, above all in the spinal column, ribs and hips. MM causes lesions in the bones called 'lytic' lesions, areas of the bone that loose their calcium content and become weak. These lesions tend to be very painful and, if sufficiently large, can lead to the fracture of the bone in question, perceived as an intense, sudden pain. Sometimes the first symptom of myeloma can be collapsed vertebrae upon lifting something that is not especially heavy, or a fracture after a minor knock.

A second frequent symptom of MM is anemia. The myeloma cells invade the bone marrow and produce substances that impede the normal production of red blood cells. This leads to anemia, which is commonly perceived as fatigue, lack of energy, and tiredness after ever less exertion. Anemia may also be suspected on account of paleness of skin, the nail beds or conjunctiva.

Although pain and anemia are the two most frequent symptoms of multiple myeloma, it must be borne in mind that pain and fatigue are two very common symptoms of a large number of diseases, including viral and bacterial infections and rheumatic illnesses. For those of an advanced age, the most frequent causes of bone pain are degenerative disorders, mainly arthrosis , and the most frequent causes of fatigue are cardiac or respiratory problems, all of which are more frequent than MM. Nevertheless, given pain that is difficult to control with analgesics, or persistent fatigue that increases over time, it is important to undergo a general analysis that includes a protein determination. In more than 95% of cases of MM it is easy to observe anomalous proteins in the blood or urine (the monoclonal component or band), and this helps guide the diagnosis and to monitor response to treatment.

Other symptoms appear less frequently, but they are very important because they may require specific treatment and should lead to an early suspicion of MM and the administration of suitable treatment. The two main ones are hypercalcemia, an increase in the level of calcium in the blood, which 13% of patients present at the time of diagnosis, and kidney problems, presented by 19% of patients. Kidney problems and hypercalcemia are detected in basic blood tests. Their clinical manifestations are not very specific and include loss of appetite, somnolence, lack of energy and constipation, but they can also include more alarming symptoms such as nausea, vomiting, and somnolence that can lead to stupor or coma. In such cases the usual reaction is to seek immediate attention. In a basic emergency blood test the problem can be easily identified. Renal problems and hypercalcemia both require immediate treatment even if MM has not yet been diagnosed.

It is very unusual for myeloma to cause fever, although it is quite common for myeloma to be diagnosed at the same time as an infection. In fact, it is important to suspect an immune disorder or MM in someone who has suffered more than one serious infection within a few months, especially if they have no known illness that would explain it.

Myeloma can also manifest itself as a swelling, or tumour with a hard consistency, that usually grows from an area of bone such as the cranium, a rib or the sternum. When such masses originate from the vertebrae they tend not to be visible or palpable since they grow inwards, but they can cause compression of the spinal cord or the nerve roots that emerge from it. This causes serious manifestations such as the loss of strength or feeling in the legs, loss of sphincter control (urine retention). Such manifestations are relatively infrequent, but if they appear they require urgent medical attention.

Sometimes it can take some time before MM is diagnosed, above all because the initial symptoms are not very alarming and are easily attributable to other causes (back ache, fatigue, etc.). Nevertheless, it is important for the presence of a myeloma to be suspected in the event of pain that can not be controlled with the usual analgesics. Vertebral compression, for example, even in the case of older people, requires a basic study that includes, at least, a basic blood test and imaging tests. If the blood test shows anemia, higher than normal levels of proteins, alterations in renal function, or an increase in the level of calcium in the blood, MM must always be suspected. MM must also be suspected if the imaging tests show 'lytic', or bone lesions typical of the disease, or fractures not caused by a previous injury.

When suspicion exists, MM diagnosis is relatively straight forward. Two essential tests need to be performed: a complete analysis of the proteins in the blood and urine in order to correctly characterise the monoclonal component, and bone marrow aspiration, to confirm the presence of abnormal plasma cells in the bone marrow. These two tests are sufficient to confirm a diagnosis for MM. It is important to complete the diagnosis with other important tests to determine the prognosis and appropriate treatment. The number and location of bone lesions must be determined by means of a radiological study of the entire skeleton. A computed tomography scan (CT scan) enables lesions to be seen in areas where X-rays are insufficiently sensitive; magnetic resonance imaging (MRI) enables a better evaluation of the vertebral column and is especially useful if there is a suspicion of spinal cord compression or myeloma mass (plasmacytomas) next to the vertebrae; and a positron emission tomograph (PET-TC) can detect lesions in other areas, although it is not always necessary to conduct all these tests.

The puncture and aspiration of the bone marrow must obtain a sufficient number of cells to perform genetic studies (there are genetic alterations that imply a worse prognosis that it is of interest to detect), and flow cytometry studies (to identify characteristics of the myeloma cells that will facilitate the monitoring of the residual disease after treatment).

Myeloma is a disseminated disease that affects the whole skeleton. Consequently, unlike other cancers, staging is not used to distinguish localised disease from differentiated disease. The measurement of two parameters in the blood (albumin and beta2-microglobulin) enables myelomas to be classified in three stages with different “quantities of myeloma” and with different prognoses.

What prognosis does multiple myeloma have?

MM is still considered to be an incurable disease. Most patients will suffer a relapse after initial treatment for the disease and will need to be treated again, probably on several occasions. This does not mean that the prognosis is very bad, in fact it is extremely variable. A small number of patients (up to 10%) will have an excellent response to first line treatment and it is possible that they may never suffer a relapse. Such patients are called "functionally cured" because it is not possible to be sure that the MM will never reappear, even after 10 or 15 years of being free of the disease. At the other extreme there are 10-15% of patients who may be resistant to initial treatment or who, while responding well initially, soon suffer a relapse. Life expectancy in such cases is very bad, at around two years. Between these two extremes are most patients, who respond adequately to initial treatment, and whose symptoms disappear or are greatly improved after the first weeks of treatment and whose life expectancies exceed the short and near-medium terms.

The long-term prognosis is, however, more uncertain because it depends on the frequency and aggressiveness of any relapses. Even when they have similar life expectancies, patients who suffer relapses that are not very aggressive and who have a good tolerance to treatment can have an excellent quality of life for years, while others, who suffer aggressive relapses, or who have poor tolerance to the various drugs used in treatment, can suffer from consequences that diminish it significantly. It is therefore a disease with very variable diagnoses and, although a large part of the initial diagnosis is focused on attempting to determine the type of MM in question, there is no adequate test for predicting an exact prognosis for either quality of life or life expectation. The initial clinical behaviour of the MM and, above all, the response to first treatment, provide a great deal of prognostic information. Patients who present a very long-lasting response to first treatment, tend also to respond well to second and successive treatments, and in such cases it is possible to consider MM as if it were a chronic disease. The situation is totally different for patients who relapse very soon after treatment, or who relapse very brusquely, and who require another treatment immediately. Brusque relapses help lead to other consequences (especially kidney failure and bone lesions) which not only affect the quality of life, but also often reduce the options available for future treatment.

It is important to anticipate and avoid the consequences of the disease and the problems associated with the toxicity of the treatments by rigorously monitoring MM patients, whether they are receiving active treatment, or whether they are in a period during which they are free of symptoms.

How is multiple myeloma treated?

The first treatments for myeloma date from the 1970s and were based on a combination of corticoids in combination with a group of chemotherapy agents called alkylating agents. These agents still form an indispensable part of treatments for myeloma but, since the end of the last century, the addition of other drugs has changed the prognosis for the disease very significantly. These new drugs belong mainly to two families, those called “immunomodulators” (thalidomide, lenalidomide, pomalidomide), and “proteasome inhibitors” (bortezomib, carfilzomib, ixazomib). They are not considered to be chemotherapy agents in the conventional sense, but that does not mean that they do not also have undesirable side effects. In general, none of these drugs is employed in isolation, their combined use hinders the MM from developing resistance and enables the symptoms to be more rapidly controlled. In general, a more intense and prolonged treatment with a combination of drugs leads to greater effectiveness and a longer response. However, the intensity and duration of the treatment must be modulated to avoid excess toxicity. Personalisation of the treatment will therefore depend on the ability of the patient to tolerate more or less intensive treatments. In this respect, age is a very relevant factor, although not the only one to be considered.

With relatively young patients (65 to 70 years of age) in a generally adequate state of health the most intensive treatment possible is attempted, including an autologous transplant of bone marrow hematopoietic progenitors. The reason for this is that the alkylating agents (specifically one that is habitually used to combat myeloma, melphalan) are very toxic for bone marrow cells. The use of melphalan in high doses increases its effectiveness, but it also irreversibly destroys many healthy cells in the bone marrow and so, in order to administer high doses of melphalan it is necessary to have previously collected progenitor cells from the bone marrow, administer the high doses of melphalan, and then proceed to reinfuse the healthy cells so that the blood cells can recover. Standard treatment for young patients, or patients without other serious health problems, may be a combination of immunomodulators, a proteasome inhibitor and a corticoid during 4 - 6 cycles (induction treatment) followed by a high doses of melphalan with an autologous transplant of progenitors and, if possible, the addition of even more treatment after the transplant (consolidation, or maintenance, treatment).

Patients for whom a transplant is not advisable on account of excessive toxicity are generally treated with a combination of three drugs, which may also include melphalan, but at a lower doses, or combinations of only two drugs that always include a proteasome inhibitor, an immunomodulator, or both. Whatever the case, treatment must be tailored to the patient's fragility in order to avoid excess toxicity. The maintenance of treatment may be attempted with two drugs, or with three at reduced doses, or spaced out in a continuous way in order to obtain results near to those obtained with more intensive treatments.

Treatment for relapse also tends to be with a combination of two or three drugs. When deciding on treatment it is important to consider: the response to previous treatments (treatments administered previously may only be repeated if they obtained good results); the toxicity of previous treatments (drugs that have already produced too much toxicity must be avoided); the characteristics of the relapse and the options for future treatment in the event of failure.

In conclusion, there are a number of useful drugs for the treatment of MM, but it is important to carefully personalise the treatment in accordance with the patient's age, characteristics and those of the disease.

Living with a myeloma: diet and care

Treatments for myeloma have toxicity and this must be monitored and anticipated, but it does not prevent patients from leading a practically normal life. There are two aspects which the patient must keep watch for: infections and bone lesions.

Myeloma patients have 10 times the chance of suffering from an infection than a healthy person. This risk is even higher when the myeloma is not under control, at the initial phase of any treatment and, above all, when the myeloma is at an advanced stage. Even so, patients whose MM is under control and who currently require no treatment still have a higher risk of infection than other, healthy, people. Infections of the respiratory system are the most frequent and also, potentially, the most serious. The risk of infection can not be prevented, but certain basic measures help to reduce the number of episodes: heightened levels of personal hygiene; the avoidance of direct contact with family and friends with active infections; and the avoidance, insofar as possible, of large groups of people during periods when influenza is prevalent. Frequent washing of the hands is the most important measure for avoiding transmission through contact in special situations (such as hospital waiting rooms) and, during periods of special sensitivity (just after a transplant, for example) it might be recommended to wear a mask to avoid the transmission of germs through the air. Other simple measures include a balanced and varied diet (vitamin supplements etc. are not necessary), good hydration, moderate exercise (especially outdoors) and the avoidance of tobacco and smoky environments.

Recovery from bone lesions caused by MM is slow, and bone fragility should be considered to be permanent, even after successful treatment. It is important to prevent vertebral compressions by avoiding the lifting or carrying of heavy items. Moderate exercise strengthens the muscles and encourages bone recalcification, but contact sports and others that involve brusque or violent movements are not recommended due to the risk of fracture. Although one of the symptoms of myeloma is hypercalcemia (an excess of calcium in the blood) foods rich in calcium (cheeses, dairy products) are highly recommended. Treatment for myeloma often includes the administration of drugs called biphosphonates which help the bones recover by capturing calcium from the blood stream. For this reason, and because the levels of calcium in their blood is often low, patients with myeloma who are being treated with biphosphonates are recommended to follow a diet that is rich in calcium, including calcium and vitamin D supplements.

Links of interest concerning medical issues relating to multiple myeloma

For more quality information about multiple myeloma, you can consult the following websites:


Links of interest about other general issues that may be of interest to patients with multiple myeloma

There are other resources and links of interest that may be of use to multiple myeloma patients:


Help and support

If you are suffering from myeloma you can access the Josep Carreras Foundation's patients' and former patients' forum a group of people who support each other to help live through this situation in the best possible way. You can access the forum here.

On our website you will also find the testimonies of people who are suffering, or who have suffered, from this disease. We would also like to invite you to follow us on our main social networks (FacebookTwitter e Instagram) where we often share patients' accounts of overcoming the disease.

If you are resident in Spain, you can also contact us via email [email protected] so that we can help put you in contact with other patients who have overcome this disease.

You will find many other topics of interest about diet, fertility, treatments, etc., on our BLOG 'Unstoppable against leukaemia'.

Webpage updated 06/30/2020 14:04:05