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.

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.

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.

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.