Multiple myeloma

Factsheet

Definition:

Multiple myeloma is a cancer that develops from plasma cells. Plasma cells are a type of white blood cell made in the bone marrow. These cells are part of the immune system and their function is to produce antibodies which protect us from infections.

Diagnosis:

Specific symptoms such as fatigue, more frequent infections, bone pain or spontaneous fractures can be present at diagnosis.

The tests that are necessary to make a diagnosis are:

  • Detection of monoclonal protein (an antibody produced by plasma cells in patients with multiple myeloma) in the blood or 24-hour urine samples;
  • Bone marrow aspirate or biopsy to measure the percentage of myeloma cells in the bone marrow;
  • Evaluation of bone lesions may be performed by your doctor. This can be done by either a magnetic resonance imaging (MRI), a whole body low dose radiation computed tomography (CT) scan or positron emission tomography (PET).
  • Blood tests to assess kidney function and levels of calcium and haemoglobin.
Treatment:

Treatment is only required in case of symptomatic disease (in the presence of hypercalcemia, kidney problems, anaemia or bone lesions) or high risk asymptomatic disease.

First line treatment is divided into two groups:

  • Patients in good physical condition who are suitable for autologous transplant : 4-6 cycles of bortezomib-based chemotherapy followed by high dose melphalan and autologous transplant as part of disease reduction after consolidation.
  • Patients with significant comorbidities or who are not physically fit enough to undergo autologous transplant :  oral combinations of melphalan and prednisone plus newer drugs are the standard treatments in this setting. In this case there is no need for further therapy after the end of the planned cycles of treatment.

Relapsed and refractory disease treatment:
The choice of treatment depends on several parameters regarding the patient (age and health status) and previous therapies. Autologous transplant can still be an option. Allogeneic transplant should be carried out only in the context of clinical trials.

Enrolment in clinical trials is strongly recommended for both first line and subsequent treatments since there are several newer active drugs currently being tested.

Follow-up:

Since multiple myeloma is characterised by recurrent symptoms, a long term follow-up is necessary to detect disease relapse as quickly as possible to avoid organ damage.

Blood and urine tests should be carried out every 2-3 months. Radiological exams and bone marrow examination should be done with individual evaluation.

If the multiple myeloma comes back, the goal is to obtain a further response by choosing between different available therapies.

Introduction

Definition of Multiple Myeloma

Multiple myeloma is a cancer of plasma cells. These are a type of white blood cell which originate in the bone marrow. The function of plasma cells is to produce antibodies. Antibodies occur naturally in our immune system and help protect us from infections caused by agents such as bacteria or viruses. When plasma cells grow in an uncontrolled way it suppresses the growth of other bone marrow cells. This can lead to conditions such as anaemia, bleeding disorders, infections and bone lesions.
In most cases there is also an abnormal production of non-functional antibodies called monoclonal protein. In multiple myeloma a large amount of a single type of abnormal antibody is produced which has no useful role in the body.

In most cases, treatments can induce long intervals without any symptoms of the disease allowing patients to have a good quality of life. Therefore, multiple myeloma can be considered as a chronic condition.

Illustration of bone marrow where plasma cells are made: normal plasma cells and abnormal plasma cells of multiple myeloma are shown.

Frequency

Is Multiple Myeloma frequent ?

Multiple myeloma is not as common as breast, colon, lung or prostate cancer but it is considered to be the second most common blood cancer after Non-Hodgkin lymphomas.
Its incidence increases with age, thus it is considered a disease of the elderly.
The probability that a person in Europe will develop multiple myeloma during his or her lifetime is 0.31%. This means for example, in Europe, 4 to 6 cases will be diagnosed among 100 000 people every year. The incidence is lower for women. Median age at diagnosis is 72 years. Incidence rates are higher in people of Afro-American origin and lower in Asians.
 

Causes

What causes Multiple Myeloma ?

Today the causes of multiple myeloma are not clear. Some risk factors* have been identified. A risk factor increases the chance of cancer occurring, but is neither necessary nor sufficient to cause cancer. A risk factor is not a cause in itself.
Some people with these risk factors will never develop multiple myeloma and some people without any of these risk factors may develop multiple myeloma.

The main risk factors of multiple myeloma are:

  • Monoclonal Gammopathy of Uncertain Significance (MGUS): most multiple myelomas arise from a benign condition known as MGUS. People affected by this condition have a little abnormal production of monoclonal protein without any symptoms. The majority of people with this condition will never develop symptomatic multiple myeloma. In most cases MGUS is discovered by accident during routine blood tests
  • Older age: the chance of developing multiple myeloma increases with age.
  • Genetic predisposition: the incidence of multiple myeloma is slightly different between ethnicities. In addition, female sex is a modest protective factor in multiple myeloma.
  • Environmental factors: radiation exposure, benzene and insecticides have been associated with multiple myeloma. These associations have a minor role in the development of multiple myeloma.

Besides the presence of MGUS and age, the evidence for all the other risk factors has not been proven.

 

Diagnosis

How is Multiple Myeloma diagnosed ?

Multiple myeloma often arises from MGUS. If MGUS is present, patients are monitored by a doctor. If MGUS progresses and develops into multiple myeloma prompt treatment can prevent the development of disease symptoms.

Symptoms characterising multiple myeloma

Symptoms caused by bone marrow infiltration:

  • Fatigue: this is the physical feeling of being tired even after rest. It is related to anaemia (low level of haemoglobin) and to the abnormal presence of multiple myeloma in the body.
  • Bone pain and fractures: sometimes progressively intense bone pain is present which rarely responds to common painkillers. This pain is often felt in the spine, ribs or hip bones and could be a result of bone fractures.
  • Infections: infections may occur more frequently and these infections may take longer to heal than in the past in the same person. This is related to both a decreased white cell count and the abnormal function of plasma cells.
  • Bleeding: rarely, abnormal bleeding may occur (for example, when brushing your teeth) or you may notice that bruising or haematomas occur more easily. This is related to low platelet count and to abnormalities in mechanisms responsible for stopping the bleeding because of monoclonal protein in the blood.

Symptoms or signs related to excessive monoclonal protein production:

  • Mild to severe kidney problems: this condition is caused by direct damage from monoclonal protein filtered by the kidneys. Usually this condition does not cause symptoms until the damage is severe.
  • Amyloidosis : this is caused by abnormal accumulation of monoclonal protein in specific sites of the body (heart, kidney etc.). The abnormal stores of the protein can cause chronic inflammation and organ damage.
  • Peripheral neuropathy: this is a result of nerve damage caused by monoclonal protein. Sensory disturbances (tingling, altered heat perception in hands and feet etc.) are the most common symptoms. 

The diagnosis of multiple myeloma is based on the following examinations:

Detection of monoclonal protein in the blood or 24-hour urine samples: this is obtained by a test called protein electrophoresis. Other tests are then performed, such as immunofixation (to identify the types of monoclonal protein present), and tests to measure the levels of serum free light chain.

The percentage of myeloma cells in the bone marrow is analysed using a bone marrow aspirate and/or biopsy. Both procedures are minimally invasive, and last for about 10-15 minutes. Local anaesthesia is used before the procedure and a mild burning sensation should be expected. The samples obtained are necessary to quantify the percentage of plasma cells present in the bone marrow and to perform genetic tests, such as Fluorescence In situ Hybridization (FISH). These tests are helpful as they provide additional information on the prognosis of the disease which is important since it could influence the choice of treatment. 

Evaluation of bone lesions : a complete radiological skeletal bone scan is necessary to identify possible fractures or areas of disease infiltration. Magnetic resonance imaging (MRI) of the spine and pelvis is more sensitive than X-ray in detecting bone lesions. This is helpful to identify lesions when they are not yet causing symptoms. A whole body low dose CT scan or a PET scan may also be needed to evaluate bone lesions.

Blood tests: complete blood cell count*, calcium, creatinine*, albumin* and beta-2-microglobulin* levels are all necessary to examine if the disease is symptomatic* and for prognostic* reasons.

These tests allow differentiation between three conditions:

Monoclonal Gammopathy of Uncertain Significance (MGUS): a benign condition which rarely develops into multiple myeloma and is characterised by serum monoclonal protein < 3g/dl; tumoural bone marrow plasma cells <10%; normal calcium levels, normal kidney function, normal haemoglobin levels and no bone lesions.
Asymptomatic (smoldering) multiple myeloma: a pathologic condition which progresses to multiple myeloma at a rate of 10% per year over the first 5 years following diagnosis. It is characterised by serum monoclonal protein >3g/dL or urinary monoclonal protein >500mg/24 hour and/or tumoural bone marrow plasma cells 10-60% without any multiple myeloma defining events (listed in the table below) or amyloidosis.
Multiple myeloma: the symptomatic condition which requires treatment. It has the same features of asymptomatic (smoldering) multiple myeloma plus multiple myeloma defining events (listed in the table below).

Multiple Myeloma defining events Definition
Hypercalcemia Serum calcium >1mg/dL higher than the upper limit of normal or >11mg/dL
Kidney problems Creatinine clearance <40mL per min or serum creatinine >2mg/dL
Anaemia Haemoglobin value of >2g/dL below the lower limit of normal or <10g/dL
Bone lesions One or more bone lesions on skeletal radiography, CT, PET-CT or MRI
Bone marrow plasma cells excess Tumoural bone marrow plasma cell percentage >60%

Very high serum free light chain ratio

Involved: uninvolved serum free light chain ratio >100

 

Treatment

What is it important to know to get the optimal treatment ?

To choose the best treatment, the doctor needs to consider many aspects, taking into account both the patient and the multiple myeloma.

Relevant information about the patient

General health status: this has to be evaluated with specific scores related to your daily activities. There are other physical factors that also have to be evaluated before starting treatment:
1. heart function (electrocardiogram and echocardiography)
2. respiratory function (pulmonary function tests)
3. liver and kidney function (blood tests)

Personal medical history: knowing relevant past or current health issues, such as previous surgical procedures or chronic diseases (diabetes, atrial fibrillation, viral infections etc.), is necessary to choose the correct treatment.

Age: even if age itself should not be considered as the only criterion to judge the general status of a patient, there are standard age limits which are used to decide if a patient could be eligible for a more intensive therapy. Usually, being younger than 65 years allows patients to receive intensive therapy, while being older than 70 years excludes them from this option. For people between 65 and 70, this decision depends upon their general health status.

Relevant information about the multiple myeloma

Treatment for multiple myeloma is not necessary when there are no symptoms.
Disease staging and cytogenetics are not necessary for asymptomatic (smoldering) multiple myeloma.

Staging
Information about the stage of the disease is necessary when multiple myeloma is symptomatic and treatment has to be started.
The information about stage is important to select the right treatment. The lower the stage, the better the prognosis. The International Staging System (ISS) is a very helpful score used for this disease. It relies only on the serum levels of albumin and beta-2-microglobulin.

Stage Definition
Stage I Serum beta-2-microgloblulin <3.5 mg/dl and serum albumin > 3.5 g/dl
Stage II Not stage I or III
Stage III Serum beta-2-microglobulin > 5.5 mg/l

 

Cytogenetics gives additional important information regarding prognosis as it is known that some genetic abnormalities are associated with a poorer outcome.

How to measure response to therapy

Therapy efficacy is measured by reduction of monoclonal protein, measured in blood serum or urine. Further tests, e.g. bone marrow evaluation, may be done on an individual basis if your doctor thinks they are necessary or if you are undergoing treatment as part of a clinical trial.

Type of response Definition
Stringent complete response Disappearance of monoclonal protein in serum or urine (immunofixation negative, normal free light chain ratio, absence of tumour plasma cells in the bone marrow)
Complete response Disappearance of monoclonal protein in serum and/or urine (immunofixation negative, abnormal free light chain ratio, <5% plasma cells in bone marrow)
Very good partial response 90% or greater reduction in serum protein plus urine protein <100mg per 24 h or serum and/or urine protein detectable by immunofixation but not with electrophoresis
Partial response

> 50% reduction of serum protein and reduction in 24 h urinary protein by >90% or to <200mg per 24 h

In patients without measurable serum and urine monoclonal protein levels, the difference between involved and uninvolved free light chain levels can be used

In patients without measurable serum and urine monoclonal protein levels and without measurable involved free light chain levels, bone marrow plasma-cell percentage can be used

Appearance of a new bone lesion(s) or increase of existing lesion(s) if this is the only measure of disease

Minimal response As for partial remission but serum or urine protein reduction comprised between >25% but <49%
Stable disease Response criteria not fulfilling definition of complete response, very good partial response, partial response, minor response
Progressive disease

Any one or more of the following criteria
Increase of 25% from lowest confirmed response value in one or more of the following criteria:
Serum monoclonal protein or urine monoclonal protein.
In patients without measurable serum and urine monoclonal protein levels, the difference between involved and uninvolved free light chain levels can be used
In patients without measurable serum and urine monoclonal protein levels and without measurable involved free light chain levels, bone marrow plasma-cell percentage can be used
Appearance of a new bone lesion(s) or increase of existing lesion(s) if this is the only measure of disease
Increase in circulating plasma cells if this is the only measure of disease

 

What are the treatment options ?

There are three questions to consider when selecting a treatment for multiple myeloma:
1) Is the disease localised in only one place without general involvement of the bones?
2) Is the disease symptomatic?
3) Is autologous stem cell transplantation an option?

Answering these questions will help to decide which treatment to choose and when it should be started.

1. Is the disease localised in only one site without general involvement of the bones ?

In some rare cases, there is just one single localised site (for example, femoral bone lesion) of the body affected by abnormal plasma cells. In this scenario, which is called solitary plasmocytoma, a systemic treatment is not required. The therapy of choice is radiotherapy or surgical excision of the lesion. Thereafter, a strict follow-up is required since this condition often evolves into multiple myeloma.

2. Is the disease symptomatic ? Are symptoms present?

If the disease is asymptomatic (smoldering myeloma), a strict follow-up, usually without treatment, is required. Once there is evidence of multiple disease sites (diffuse bone marrow involvement or multiple bone lesions), it is crucial to understand if there are signs and symptoms of disease. A systemic treatment* has to be started if the disease is symptomatic.
The treatment will usually include therapies that:

  • treat multiple myeloma systemically (treating myeloma cells throughout the body).  
  • treat multiple myeloma locally (i.e. in specific sites of the body), such as surgery or radiotherapy if symptomatic bone lesions are present (e.g. backbone fractures).

3. Is autologous stem cell transplantation an option?

Autologous stem cell transplantation (with the patient’s own stem cells) gives the best disease responses when incorporated in the first-line of therapy. Even if it is now less toxic than in the past, this is reserved only for younger patients and those patients in good physical condition who can tolerate the side-effects of the procedure. Being older than 70 usually excludes patients from undergoing stem cell transplantation. An exception might be made if an older patient is in good physical condition without other relevant health issues. This depends on an accurate clinical evaluation of each case.

Treatments listed below have their benefits, their risks and their contraindications. It is recommended that you ask your doctor about the expected benefits and risks of every treatment in order to be informed about the consequences of the treatment. In cases where several treatment options are available, the choice should be discussed according to the balance between benefits and risks.

First-line treatment plan for autologous stem cell transplantation candidates

Patients in good physical condition (or those younger than 65) who are candidates for autologous stem cell transplantation usually receive an induction treatment. The aim of this is to reduce the disease burden before the transplantation. Once the disease burden is reduced, the goal is to maintain a response for as long as possible with an autologous transplant.
Induction treatment is usually composed of a three-drug regimen:

  • Bortezomib (V)/thalidomide (T)/dexamethasone (D) (VTD)
  • Bortezomib (V)/cyclophosphamide (C)/dexamethasone (D) (VCD)
  • Bortezomib (P)/doxorubicin (A)/dexamethasone (D) (PAD)
  • Lenalidomide (R)/bortezomib (V)/dexamethasone (D) (RVD - this combination is not approved yet in Europe).

One treatment cycle usually lasts 21 or 28 days. Response to treatment is assessed before each cycle. The total number of cycles required to complete the induction treatment ranges from 4 to 6, depending on the type of response, therapy and your health status.
After the induction therapy, a consolidation phase is necessary to prolong the interval that patients remain free from disease. In multiple myeloma, consolidation is obtained with autologous stem cell transplantation. This process is preceded by the collection of autologous (of the patient) stem cells by a procedure called apheresis. To stimulate the release of stem cells from the bone marrow to the bloodstream, the patient receives a growth factor (granulocyte-colony stimulating factor, G-CSF) alone or in combination with chemotherapy (cyclophosphamide). After a few days, when the number of stem cells rises, the patient receives the apheresis procedure. The number of stem cells can be determined by means of blood tests. Peripheral blood is filtered and stem cells are collected and frozen. Once the collection has been done and the patient has recovered from the procedure, he or she can be admitted for the autologous transplantation. This procedure consists of administering high dose chemotherapy (usually with a drug called melphalan) followed by reinfusion of the patients’ own stem cells.
If the first transplant does not give a complete or almost complete response, a second autologous transplantation can be performed usually within 3-6 months after the first.

Allogeneic stem cell transplantation (from a donor) should only be carried out in the context of a clinical trial.

First-line treatment plan for NON transplant candidates

Patients who are not candidates for autologous stem cell transplantation (70 years and older or patients in poor physical condition) are usually treated with a three-drug induction regimen. Frailer patients can be treated with a two-drug regimen.

Three drug regimens:

  • Bortezomib (V)/melphalan (M)/prednisone (P) (VMP)
  • Melphalan (M)/prednisone (P)/thalidomide (T) (MPT)

Two drug regimen:

  • Lenalidomide (R)/dexamethasone (D) (RD) 
  • Bendamustine/prednisone
  • Melphalan/prednisone
Second-line treatment plan for relapsed or refractory disease

Participation in clinical trials should be encouraged to allow patients to benefit from new drugs or combinations of drugs which are currently being tested.

Considerations that should be taken into account when choosing first-line treatment still apply to second-line or subsequent therapies. Choice depends on several factors regarding the patient (age, health status) and previous treatments (type, efficacy, tolerance).

The following therapies can be used in this setting:

  • Lenalidomide/dexamethasone
  • Pomalidomide/dexamethasone: only for patients who have already failed on lenalidomide and bortezomib
  • Bortezomib alone or in combination with dexamethasone or pegilated doxorubicin
  • Carfilzomib/lenalidomide/dexamethasone or carfilzomib/dexamethasone
  • Ixazomib/lenalidomide/dexamethasone: only for patients who have already failed one of previous therapies
  • Panobinostat/bortezomib/dexamethasone: only for patients who have already failed on bortezomib and an immunomodulatory drug (thalidomide, lenalidomide, pomalidomide)
  • Elotuzumab/lenalidomide/dexamethasone
  • Daratumumab alone for patients who have already failed on proteasome inhibitors (bortezomib, carfilzomib, ixazomib) and immunomodulatory agents (thalidomide, lenalidomide, pomalidomide), and in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.

Autologous stem cell transplantation could also be used in selected cases (in those with good response to previous autologous transplant and with disease response of longer than 2 years).

Allogeneic stem cell transplantation (from a donor) should be carried out only in the context of a clinical trial.

Treatment of multiple myeloma complications

It is very important for the treatment of multiple myeloma to cure its organ-related complications.
Timing is fundamental to prevent chronic organ damage or life-threatening events.

Impaired kidney function: almost fifty percent of patients affected by multiple myeloma have impaired kidney function. Treatment may vary depending on the grade of kidney impairment. Along with systemic therapy, oral and intravenous hydration or even dialysis could be part of the treatment. It is fundamental to avoid the use of non-steroidal anti-inflammatory drugs, such as aspirin or nimesulide, as they may cause kidney damage.

Bone pain or bone lesions: bone damage is frequent in multiple myeloma. It can be asymptomatic or it may cause pain. In some cases, bone fractures can be the initial manifestation of multiple myeloma and in this case an orthopaedic intervention is necessary. Besides surgical intervention, radiotherapy can also be useful.

If bone lesions are not present but there are early signs of bone erosion, a therapy with bone strengthening drugs is suggested. Bisphosphonates are the main drugs used for this purpose. Zoledronate or pamidronate are given by intravenous infusion. This treatment should be done for two years and infections of the jaw should be excluded before starting these drugs.

Increased blood calcium level: this is due to bone erosion. The extent of the increase can vary. Intravenous fluids and bisphosphonates are required in case of very high calcium levels.

Anaemia: this is related to low red blood cell count. There are several causes of anaemia in multiple myeloma. Bone marrow infiltration by abnormal plasma cells and/or kidney damage are the most frequent causes. Blood transfusions can be necessary in very severe cases. Administration of erythropoietin, a drug which stimulates red blood cell production, may decrease the need for transfusions.

Infections: both chemotherapy and multiple myeloma can weaken the immune system. For this reason, your doctor may give you some anti-infective drugs to prevent infection. In case of fever or other signs of infection, do not hesitate to contact your doctor as it could be important to start the correct treatment. The influenza vaccine is helpful in decreasing the rate of respiratory infection.

Spinal cord compression: the cause of this complication is the presence of a localised mass (plasmocytoma) at backbone level which compresses the spine. This can also be caused by backbone fractures. Symptoms are localised pain or nervous symptoms such as tingling in the legs or muscular weakness. You should seek medical attention immediately if you experience these symptoms as this complication can lead to irreversible paralysis if not treated. Corticosteroids, radiotherapy or even surgery are therapies available to treat this condition.

What are the possible side effects of the treatments?
 

Side effects vary according to treatment type. A few of the most common side effects caused by multiple myeloma therapies are as follows:

  • Appetite loss: some treatments may cause appetite loss which can last for a few days after the treatment ends or sometimes longer. Try to eat smaller meals more often than usual, since they are easier to digest. Avoid fatty foods and drink plenty of liquids (approximately 1.5-2 L/day).
  • Constipation: some drugs, such as thalidomide, bortezomib or dexamethasone, can cause constipation. This is a very common symptom and your doctor can prescribe special medication (laxatives) in case this occurs. It is very important to prevent constipation. If constipation is present, drink plenty of liquids (2 litres/day of water/soda/tea etc.) and include exercise in your daily routine.
  • Diarrhoea: this symptom can be related to certain drugs, such as lenalidomide, or bortezomib, or to an unrelated infection. There are several remedies that can be used depending on the cause of the diarrhoea. It is important to notify your doctor if this occurs.
  • Hair loss: older chemotherapy drugs can cause hair thinning or loss. Depending on the therapy, it may last until therapy is completed. Once the treatment is finished, your hair will grow back.
  • Infertility: Alkylating agents, such as melphalan (used for autologous transplantation) and cyclophosphamide (used for stem cell collection), are more likely to cause this side effect. If you are taking thalidomide or lenalidomide, teratogenic effects may occur. If you are planning to have children or this could be an option in your future, remember to ask your doctor about this issue. Today there are some ways to reduce the chance of becoming infertile and to collect sperm or eggs before starting treatment.
  • Infections: virtually all chemotherapy agents can increase the incidence of infections. This happens because of a reduced number or altered function of white blood cells. These cells defend our body from bacterial, viral or fungal infections. Bacterial infections and viral reactivations are the most common infectious complications during a treatment and in the following months after it is completed. Some drugs are usually prescribed during this phase to reduce the incidence of this complication. Neutropenia is a reduction of neutrophils, the fraction of white blood cells whose function is to protect us from bacterial and fungal infections. If you have a fever or any other symptom while you are neutropenic (with a low number of neutrophils), it is important to contact a doctor as soon as possible since it is possible to develop a severe infection requiring hospitalization. There are a few tips to follow to reduce the chances of becoming ill:
    1) Avoid crowded places: the higher the number of people, the more likely the chances of becoming ill. This is especially true during the flu season (autumn/winter).
    2) Eat healthily: this means avoiding foods that may carry infections. Follow standard hygiene rules and do not eat raw meat or fish/seafood or unpasteurised dairy products.
    3) Stay active: doing light physical activities, such as walking, can help you recover from chemotherapy-related fatigue and it will keep your heart, lungs and muscles in good shape. This reduces the risk of infection and helps your body to cope with stressful conditions.
  • Nausea and vomiting:  this side effect is usually related to traditional chemotherapy agents. Antiemetic agents are commonly used to prevent this side effect. Sometimes, if prevention is not enough, other drugs can be prescribed to treat nausea and vomiting.
  • Peripheral neuropathy: this is commonly related to bortezomib and thalidomide. Damage to peripheral nerves can cause both sensory deficit (palms and soles tingling) and pain. This damage usually arises gradually, starting with feet and hands. It is important to tell your doctor if you have any of these symptoms. Adjusting drug dosage and how the drug is administered (subcutaneous instead of intravenous bortezomib) is usually sufficient to reduce or stop these symptoms. There are a few drugs available to reduce peripheral neuropathy.
  • Thrombosis: the risk of developing a blood clot is higher when thalidomide or lenalidomide are combined with dexamethasone*. Swelling, pain and occurrence of a red warm area are signs and symptoms of thrombosis. If you notice this in your arms or legs, contact your doctor immediately. To reduce the chance of thrombosis, a prophylaxis with anti-coagulant drugs (heparin or low-dose aspirin) is usually prescribed and may be recommended when the above combinations are used.

 

What happens after the treatment ?

 

Follow-up with doctors
In patients with multiple myeloma, a long term follow-up is necessary to detect disease relapse before it becomes symptomatic.
Blood tests, e.g. complete blood cell count, measurements of creatinine and calcium levels, serum and urine electrophoresis and/or serum-free light chain ratio determination, should be carried out every 2-3 months. Radiological exams and bone marrow examination may be done on an individual basis. 

Back to daily activities
The diagnosis of multiple myeloma may cause changes in your daily life and also in the daily activities of those close to you. Patient support groups may help you to cope with these changes. It can be hard to live with the idea that multiple myeloma can come back. Based on what is currently known, there are no specific recommendations to decrease the risk of recurrence after completion of treatment. As a consequence of the treatment and the multiple myeloma itself, return to normal life may not be easy for some people. Questions related to body-image, sexuality, fatigue, work, emotions or lifestyle may be a concern for you. Discussing these questions with relatives, friends, other patients or doctors may be helpful. Patient support groups may also be able to help by providing advice on dealing with the effects of treatments. Psycho-oncologists or telephone information services and helplines are available in many countries to provide additional support.

What if the multiple myeloma comes back?
If the multiple myeloma comes back this is called a relapse or recurrence. Treatment in this case depends on the age and health status of the patient and prior treatments.

There are currently several effective therapies available for relapsed multiple myeloma and it is of utmost importance to find the most appropriate one in terms of efficacy and toxicity. More drugs are expected to arrive into clinical practice in the next few years.

Generally, the goal of a second-line therapy for multiple myeloma is to obtain a second response, the longer the better, in order to offer the patient another period of time without disease symptoms. This could be compared to the concept of a chronic disease, such as diabetes or hypertension, where the aim of treatment is not to cure the disease itself but its symptoms. In both cases, the aim is to allow the patient to live a normal life for as long as possible.


Should I consider clinical trials?
Despite the best therapies that are currently available, the majority of patients will have disease relapse after first-line treatment. During the last few years, an increasing number of new drugs have been developed and tested world-wide. Drugs proven to be effective in laboratory experiments are eligible to be tested in humans, in what is known as clinical trials. Not all clinical trials will result in better treatment and may show that the treatment being tested isn’t as good as those already in use. However, participating in clinical trials is important as it gives patients access to drugs which would not otherwise be available for a number of years. It is important to talk with your doctor about the possibility of participating in such a clinical trial. You can also find information about clinical trials on Internet (clinicaltrials.gov, or clinicaltrialsregister.eu).

Synonyms

Multiple myeloma

Myeloma

Kahler disease

Plasma Cell Myeloma

Myelomatosis

Blood cancer

Bloodcancer

 

Therapies by type

The following list of treatments is based on what we have found in scientific studies about cancer. More information about the listed therapies can be found under the tab THERAPIES. For registered drugs, radiotherapy and surgical interventions, approval by the authorities is given.

Cell-based therapies

Administration to patients of their own or someone else’s manipulated human cells. More

Clinical trials

A clinical trial is a research study conducted with patients to evaluate whether a new treatment is safe (safety) and whether it works (efficacy). Clinical trials are performed to test the efficacy of drugs but also non-drug treatments such as radiotherapy or surgery and combinations of different treatments. Clinical trials take place in all kinds of hospitals and clinics, but mostly in academic hospitals. They are organized by researchers and doctors.

The Anticancer Fund provides a tool to search for phase III clinical trials by type of cancer and by country. For Belgium, the Netherlands, Switzerland, Luxembourg, France and the UK, the Anticancer Fund provides contacts to get more information about the phase III clinical trials currently ongoing. Discuss the possibilities of participating in one of these clinical trials with your doctor.

The list of the phase III clinical trials for multiple myeloma is available here.