Treatments or drugs are commonly used in different combinations, such as thalidomide and high dose steroids or melphalan and prednisone. In addition, a number of new and emerging treatment therapies are becoming available.
Each patient is assessed individually. What works for one patient may not work for someone else. Whatever treatment you are given, the goals of therapy are similar:
Sometimes, the best treatment is no treatment at all. If your myeloma is stable (that is to say, is not progressing or getting worse), the best option may be to simply monitor your condition. Currently, there is no evidence that treatment is beneficial for people who have MGUS or asymptomatic myeloma (smoldering or indolent myeloma), or who have been treated and are in remission. Research on the role of ongoing or maintenance therapy is being conducted and approaches may change in the future.
You may have heard these terms, but what do they mean? A first line treatment is a form of therapy that is used on people who have not had any previous treatment for their myeloma. If the myeloma does not respond (the disease is said to be refractory) or if it progresses after the first line therapy has been completed (i.e., there is a relapse), the subsequent therapy is referred to as second line treatment.
High energy radiation may be used to damage the myeloma cells and prevent them from growing. Radiation therapy is typically used on specific parts of the body to treat bone pain and plasmacytomas, usually in combination with some form of chemotherapy.
Total body irradiation was used in the preparation for autologous stem cell transplantation in the past. Clinical trials have shown that it does not improve outcome for transplant but does add to side effects. It is usually not used in conjunction with autologous transplantation anymore.
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The goal of chemotherapy is to reduce the number of plasma cells in the bone marrow and the proteins they produce. Chemotherapy cannot “cure” myeloma but it may put the disease into remission (that is to say, stop it from progressing or getting worse). It must be tailored individually to each patient.
There are many forms and combinations of chemotherapy regimens. Some of the most common in Canada are:
People with myeloma may receive their chemotherapy intravenously, in cycles of alternating treatment and rest periods. The rest periods allow patients to recover from chemotherapy-related side effects. They also increase the chances that tumour cells that are dividing will be exposed to treatment. The length and type of chemotherapy will depend in part upon whether there are plans to perform a stem cell transplant in the future.
Central line: When you are receiving chemotherapy, you may be given a central line. You may hear it referred to as a Portacath, PICC line or Hickman™. A central line is a long, hollow tube made from silicone rubber which is inserted or tunnelled under the skin of your chest into a vein. The end of the central line hangs out of the chest and is usually sealed off with a cap. The line can be left in for weeks or months and makes it possible for you to have your treatment without having to have needles inserted at each visit. When it is time for your chemotherapy, the nurse or doctor connects the line to a syringe or drip. When you no longer need chemotherapy, the line may be removed.
Steroids (corticosteroids) are chemicals naturally produced by the adrenal gland to help prevent inflammation. The synthetic or man-made steroids most commonly used to treat myeloma are prednisone and dexamethasone. Steroids can be used alone or in combination with other drugs, such as chemotherapy drugs.
Stem cells are cells that can be used to “repopulate” the bone marrow. They are normally found in the bone marrow and in the blood. There are several types of stem cell transplantation approaches that may be used to treat myeloma.
Autologous stem cell transplantation (ASCT) is the most common. It is referred to as an “autograft” because it uses your own stem cells. Stem cells can be obtained from blood in the veins (a peripheral blood stem cell or PBSCT), your bone marrow, or even from the blood of an umbilical cord (something few adults currently have access to). A transplant consists of the following steps:
Allogeneic transplant involves collecting stem cells from someone else, usually a blood relative. The donor’s cells must match the recipient’s tissue type – note that this is different from blood type and if considered requires special blood testing. The transplanted donor stem cells may also help attack any myeloma cells remaining in the patient’s bone marrow. This is referred to as the graft-versus-myeloma effect.
Few patients are good candidates for allogeneic transplant. It is difficult to find good donor matches and the procedure has a greater risk of complications, including infections, graft-versus-host disease (GVHD, a potentially life-threatening condition in which the donor’s bone marrow attacks and destroys the patient’s own tissue), and death. For these reasons, allogeneic transplant is not a standard therapy for myeloma.
There are two types of allogeneic transplant:
A syngeneic stem cell transplant refers to a transplant using stem cells taken from an identical twin. The prognosis for syngeneic transplants is better than that of allogeneic transplants; however, this is an option for only a small number of patients. A matched unrelated donor (MUD) transplant refers to a transplant using stem cells taken from a donor who is not a relative but has the same tissue type.
Tandem (double) autologous transplants are performed in some centres. For a tandem transplant, the plan is to conduct a second transplant within six months of the first one. This approach may be beneficial for people who do not have a full response to the first transplant or who have “high risk” disease, as indicated by age or genetics (cytogenetics).
An experimental approach is ASCT followed by a mini-allogeneic transplant. In this version, a patient first undergoes high-dose chemotherapy to reduce the overall number of myeloma cells, followed by an autologous transplant. Next there is a second course of moderately high-dose therapy with an allogeneic transplant of donor stem cells. The second course of therapy – in combination with the help of the allogeneic transplant –should reduce the number of myeloma cells.
The question of whether or not you should continue treatment after a transplant has not yet been fully answered. Your treatment options will depend upon your condition, preferences, and other factors. Studies are underway which will give us more information about post-transplant maintenance therapy; you may be able to participate in such a study and should discuss with your physician.
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Plerixafor is a stem cell mobilizer, which means it stimulates the release of blood cells from the bone marrow. Plerixafor. is a drug used in combination with granulocyte-colony stimulating factor (G-CSF) that is used to help collect blood stem cells for transplantation. Plerixafor blocks a protein on the surface of blood stem cells.
You will first receive a treatment with G-CSF once daily for 4 days.
Then you will be given plerixafor 10 to 11 hours before each session of apheresis (a collection of your stem cells).
The usual dose of plerixafor is 0.24 mg/kg body weight/day given to you as an injection under the skin (subcutaneous injection) for up to 4 consecutive days.
Plerixafor works by improving the release of stem cells (cells with the ability to develop into many different cell types with different functions) from the bone marrow, making them available to collect from your bloodstream. Normally, these stem cells are present in the bloodstream in very low numbers since they are more likely to stay in the bone marrow. Plerixafor increases the levels of stem cells in the blood by preventing them from remaining anchored inside the bone marrow space. The stem cells can then be collected by an apheresis machine and subsequently frozen and stored until your transplant. ?
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Thalidomide is an immunodulatory agent (IMiD). Instead of destroying myeloma cells (like chemotherapy drugs), thalidomide interferes with the underlying processes that promote the growth and reproduction of myeloma cells. Thalidomide:
inhibits factors that promote the growth of blood vessels (Vascular Endothelial Growth Factor or VEGF and basic Fibroblast Growth Factor or bFGF) that help to feed tumours;
modulates the level of several chemicals (called cytokines) that the cancer cells use to communicate with one another and orchestrate growth and reproduction (e.g., Tumour Necrosis Factor – alpha or TNF-α, interleukin 6 or IL-6, interleukin 2 or IL-2, and interferon-gamma or IFN-γ);
alters the expression of chemicals involved in acute rejection, such as cytokine secretion and cell growth.
Thalidomide is used to treat cases in which the myeloma has not responded to treatment (refractory myeloma) or has returned after treatment (relapsed myeloma). In some countries, it is also used as front-line or initial treatment. It can be used as a single agent or in combination with other drugs such as dexamethasone, prednisone or melphalan.
Bortezomib is a proteasome inhibitor, one type of the new generation of “biological treatments”. It works by acting on the myeloma cells and the cells with which they interact to inhibit plasma cell growth and reproduction and to promote cell death.
Bortezomib is given intravenously, usually four times every three weeks.
Bortezomib can be used in combination with melphalan and prednisone (VMP) as a front-line treatment for patients who are not eligible for stem cell transplantation. Patients who have relapsed after their first treatment may also be given bortezomib either alone or with other medications, such as dexamethasone and doxorubicin.
Like thalidomide, lenalidomide is an immunomodulatory agent (IMiD) but is more potent and has a different side effect profile from than thalidomide. Lenalidomide has multiple mechanisms of action that affect both the cancer cell and its microenvironment.
Lenalidomide can be used as a second-line treatment in combination with dexamethasone as a treatment for patients with who have received at least one prior therapy.
Indicated for patients with multiple myeloma for whom both Revlimid® (lenalidomide) and Velcade® (bortezomib) have failed, who have received at least two prior treatment regimens, and who have demonstrated disease progression in their last therapy.
A number of new therapies are in development. At the beginning of 2009, among the clinical trials were underway in Canada were a new proteasome inhibitor (carfilzomib), a monoclonal antibody (CNTO 328) and tanespimycin, a new class of drug called heat shock protein 90 (Hsp90) inhibitors.
Other new approaches are currently being tested. They include:
Some of these new therapies target not only the myeloma cell, but also the bone marrow microenvironment (the “neighbourhood”) in which the myeloma lives. One of the most exciting aspects of current research is the insights that are being made into the genetics of the disease. In the future, knowing more about the genetics of myeloma will make it possible to more closely individualize and tailor treatment.
For more information about new and emerging therapies, click on the “Research and Clinical Trials” tab on this website. Additional sources of clinical trial information can be found on the International Myeloma Foundation (IMF) website (www.myeloma.org, click on Myeloma Matrix) and the US National Institute of Health website (www.clinicaltrials.gov).
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