Last modified: 15-02-08

Treatment

The main aim of every tumour therapy is to largely suppress the disease. With multiple myeloma, a permanent cure is only possible for patients who are locally affected (extramedullary plasmacytoma, solitary plasmocytoma) and for younger patients following an allogenic (from another person) bone marrow transplantation. Apart from this, multiple myeloma is incurable with current treatment methods. The aim of the therapy is therefore the prolongation of life and optimisation of the quality of life.

Possible therapies for multiple myeloma

Chemotherapy

Chemotherapeutic agents are substances that inhibit the growth of tumour cells. In contrast to other malignant tumours that require immediate therapy, a multiple myeloma diagnosis does not necessarily justify an immediate course of chemotherapy. Nevertheless, chemotherapy should by all means be started

• if symptoms occur such as a reduction in physical fitness, fatigue, loss of weight or bone pains,
• if there is evidence of restricted kidney function,
• given the occurrence of hypercalcemia (high level of calcium in the blood) or
• if there are signs of increasing anaemia.

Specific cytostatic agents (medicine for inhibiting cell growth = chemotherapeutic agents), so-called alkylating agents, are particularly effective in the treatment of multiple myeloma. In some cases, alkylating agents, such as melphalan or cyclo-phosphamide, are combined with cortisone preparations.

The most frequent side effects of chemotherapy are nausea and vomiting. Further possible side effects are anaemia, inflammation of the mucous membranes, hair loss, damage to the nervous system and an increase in weight. Most of these side effects occur only during the period of chemotherapy treatment.

Your doctor will advise you as to which preparations and combinations can be considered for your chemotherapy treatment.

High dosage therapy and stem cell transplantation

Studies have shown that the use of melphalan in very high dosages has led to full remission (complete disappearance of the symptoms of the illness) with many patients. Nevertheless, the high dosage therapy had a negative effect on the bone marrow. The result is a pronounced lack of white blood cells, combined with a major risk of infection. The following procedures have now become established for high-dosage multiple myeloma therapy:

• Administering of growth factors that accelerate the regeneration of white blood cells. These growth factors are known as granulocyte colony-stimulating factors (G-CSF).
• Re-transplanting of bone marrow - or of periphery stem cells (circulating in the blood) obtained prior to the high dosage therapy. This procedure is also referred to as autologous (obtained from the own body) stem cell transplantation.

Consult your doctor as to whether this form of autologous or even allogenic (stem cells from another person) transplantation, in combination with high-dosage chemotherapy, can be considered in your case and regarding the risks associated with these methods.

Radiation therapy

The aim of radiation is to stop the ability of degenerated cells to divide and thus to prevent further growth of the tumour. Unlike many tumours, radiated healthy cells have the ability to repair the damage caused by the radiation, with the result that the radiation has a far greater effect on the tumour than on the surrounding healthy organs. It is important to know that no radioactive substances penetrate into the body during radiation therapy.

With multiple myeloma, radiation therapy is used above all for treating bone pains. In addition, radiation therapy can prevent bone fractures in supporting bone sections. Existing bone fractures can be stabilised using radiation.

Acute side effects, such as reddening of the skin, are rare. Various further side effects can occur depending on the area subjected to radiation. You should discuss these individually with your radio-oncologist and you should also discuss the form of radiation to be used in your case.

Treatment with interferon

Alpha-interferon is an active substance produced by the body that acts on the cells of the immune system. Amongst other things inferon inhibits the reproduction of plasma cells. Experience has shown that the use of inferon is to be recommended with patients for whom chemotherapy has led to a remission, or at least to a stabilising of the clinical picture. This particularly concerns high dosage therapy and stem cell transplantation patients. The aim of inferon therapy is to maintain the remission achieved through chemotherapy.

Influenza-like symptoms and episodes of depression are possible side effects.

Treatment with thalidomide

The use of thalidomide in the treatment of myeloma is a new therapeutic approach . Scientists have discovered that thalidomide can inhibit the formation of new blood vessels. The regeneration of blood vessels, also known as angiogenesis, is an indispensable prerequisite for the growth of tumours. In addition, thalidomide also appears to have an effect on the immune system. The aim of scientific research is to ascertain whether the growth of tumours can be slowed down by the use of thalidomide. Data gathered so far shows that up to 40% of pre-treated patients respond to thalidomide therapy. In the case of newly diagnosed patients, the combination of thalidomide and dexamethasone leads to remission in around 60 percent of cases, and the combination of thalidomide, dexamethasone and melphalan leads to remission for up to 80 percent of patients.

However thalidomide therapy can have side effects that not infrequently force the treatment to be broken off. Peripheral nerve damage, constipation, fatigue, a feeling of weakness and skin rashes can occur.

Thalidomide is currently used to treat newly diagnosed patients, patients in relapse or with primarily refractory disease, but also patients who have undergone successful initial therapy as maintenance treatment. However for maintenance therapy the dose needs to be greatly reduced and clear recommendations do not yet exist here. The results of trials are not yet available. (Information on clinical studies can be found here.)

Treatment with Bortezomib

Not all details of the manner of effect of this so-called proteasome inhibitor have yet been clarified. However, the following would appear certain: The formation and the breaking down of signal proteins are equally as important for the survival of the cancer cells as for the reproduction of cells, the adhesion of cells and the formation of new blood vessels. The breaking down of these proteins is controlled by so-called proteasomes. These are enzyme complexes that occur in both healthy as well as in cancer cells and break down marked intracellular proteins in a controlled manner.

Bortezomib inhibits the proteasomes, with the result that many signals in the cancer cell nullify each other reciprocally or are prevented. This, in turn, leads to the inhibiting of the tumour growth and of the formation of new blood vessels, the death of the cancer cells (apoptosis) and to the inhibiting of the interaction with conjunctive tissue cells of the bone marrow.

In Europe, Bortezomib was approved in April 2004 under the brand name Velcade® for the treatment of multiple myeloma, provided at least two preceding courses of therapy had been completed and progression of the illness had been observed during the final treatment (so-called third-line therapy). Since April 2005 Velcade® has also been approved for the treatment of patients with just one pre-treatment (so-called second-line therapy). In order to receive Velcade® as monotherapy (i.e. not in combination with another drug) patients should have already undergone a bone marrow transplantation or not be suitable for this. The optimum duration of treatment with Velcade® is not yet known.

The most frequent side effects that occurred in the clinical studies with Velcade® were moderate degrees of fatigue, a feeling of being unwell, weakness, nausea, diarrhoea, a reduced appetite and constipation. Additionally, however, there may be a reduced concentration of blood platelets, peripheral neuropathy (numb feeling, a tingling sensation and/or pain in the hands, arms, feet or legs), high temperature, vomiting and anaemia. The occasional occurrence of high temperature, pneumonia, severe diarrhoea, vomiting, dehydration and dizziness were stated as serious side effects.

Treatment with Lenalidomide

Lenalidomide has been approved in the United States, the EU and in Switzerland for a combination therapy with Dexamethasone in patients with multiple myeloma who already received a standard therapy. Since the end of 2005, Lenalidomide has also been approved in the USA for the treatment of patients requiring transfusions with myelodysplastic syndrome of risk class "low" or "intermediary-1" with simultaneous 5q-deletion with or without additional cytogenetic abnormalities.

Lenalidomide belongs to the IMiDs® substance class. This abbreviation stands for immunomodulatory drugs, meaning pharmaceutical substances that may modulate the immune system. IMiDs® are compounds derived from Thalidomide, which have much lesser side effects while having a same or better effectiveness.

So far, the effect mechanism of Lenalidomide has not been completely investigated. It is known however that the substance acts in different parts of the body. The immunomodulatory and antiangiogenetic properties of this substance affect the release of inflammatory substances and increase the production of antiphlogistics. The formation of blood vessels on tumours is inhibited. As a result, the supply of the cancer cells with nutrients is inhibited. Lenalidomide also has a direct effect on tumour cells by inhibiting their growth. Lenalidomide is therefore able to correct metabolic processes, which have become unbalanced in different parts of the body.

However, a therapy with Lenalidomide is also associated with side effects. In many cases, the blood picture also changes temporarily when taking Lenalidomide. The number of blood platelets may decrease (thrombocytopenia), as well as the number of white blood platelets (neutropenia). The results of the blood tests may necessitate an interruption of the therapy or a reduction of the Lenalidomide dose. Some patients require growth factors and/or blood transfusions.

Another side effect of Lenalidomide may be an increased risk of developing blood clots during treatment (vein thrombosis and lung embolism). There are no studies so far that clearly prove that a preventive therapy leads to a reduction of the probability of developing thrombosis. However, the physician may prescribe a prophylactic therapy against vein thrombosis or lung embolisms depending on the individual risk of developing blood clots. Other side effects that may be caused by taking Lenalidomide are diarrhoea, skin rashes and itching.

Treatment with bisphosphonates

One of the most frequent symptoms encountered by patients that ultimately leads to the diagnosis of multiple myeloma patients, is the occurrence of bone pain, in particular in the spinal column and ribs. The pain is caused by the destruction of bone material, in turn brought about by the myeloma cells. Bisphosphonates are part of the standard therapy for multiple myeloma. They can slow down the bone-destroying process.

Myeloma cells produce factors which stimulate the activity of the cells regulating the bone destruction activity (osteoclasts) and lead to increased bone resorption. It is thought that local factors play a role, which means that bone resorption is most pronounced in areas where myeloma cells are found. This mainly affects the whole spinal column, the pelvis and the pelvic girdle, but also the cranial bones, shoulders and the bony thorax. The aim of treatment with bisphosphonates is to suppress the excessive activity of the osteoclasts. Patients treated often experienced a considerable reduction in their bone pain.

Bisphosphonates are a relatively safe form of medicine. However, they can lead to influenza-like symptoms and, when used for the first time, can even cause a temporary increase in the bone pains. All bisphosphonates can cause kidney problems if infused (introduced) too quickly. Despite the absence of any long-term studies in this respect, life-long treatment with bisphosphonates is recommended for myeloma patients, whereby the kidney function must be monitored on a regular basis.

Bisphosphonates probably prevent the further destruction of bone but do not, however, lead to any regression of existing damage. Although there are no studies on this, some doctors treat their patients with bisphoshonates even in the early stages of myeloma as a precautionary measure. Laboratory studies have shown that bisphosphonates can destroy myeloma cells.

Symptoms of so-called osteonecrosis can occur from time to time with patients treated with bisphosphonates. This is bone destruction in the jaw. The results can be pain, loose teeth, sharp edges of free-lying bone tissue and the breaking off of small parts of bone. The initial symptoms are frequently swelling, a sense of numbness and pain. With oral surgery operations, the healing process can be seriously impaired. Thus far it is not known whether the type of bisphosphonate plays a role and whether other factors (for example radiation, other medicine, dental pre-treatment) have any influence.

Until such time as these questions are clarified, myeloma patients are advised to inform the dentist of their treatment with bisphosphonates if applicable. In the event of the problems outlined occurring, the treatment should be interrupted for two to four months. The use of antibiotics is recommended for treating infections in the jaw area.

Treatment of accompanying symptoms

Speak to your doctor regarding the treatment of accompanying symptoms of multiple myeloma, such as anaemia, increased brittleness of the bones, infection and pain and take corresponding precautionary measures yourself. Consult your doctor upon the first signs of complaints and inform any doctor treating you (including your dentist or eye specialist) of your illness.

Ask your doctor about matters to which you should pay special attention in terms of accompanying symptoms, always take medicine precisely as prescribed and take advantage of prophylactic inoculations. It is not correct that myeloma patients should not be vaccinated; for vaccinations with vaccines that destroy bacteria or viruses there is no greater risk to myeloma patients than to other patients.