Stages II-III Multiple Myeloma
Stage II or III multiple myeloma is characterized by an intermediate or high amount of cancer in the body. Patients with these stages of multiple myeloma typically have bone complications as a result of their disease and usually experience symptoms that require treatment.
With current therapy, curing patients with multiple myeloma is uncommon; recent advances in treatment, however, have prolonged survival by several years. The only potentially curative treatment for multiple myeloma remains high-dose therapy followed by a stem cell transplant using donor cells (allogeneic stem cell transplant). This treatment, however, is associated with significant side effects and is only appropriate for younger patients or those who have failed other therapies.
There are a large number of effective chemotherapy drugs now available for initial, standard-dose treatment of patients with multiple myeloma. The main goal of initial therapy of multiple myeloma is to produce a complete or near complete disappearance of myeloma cells in the body. Approximately 30-50% of patients can expect to achieve this goal.
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About this Treatment Information
The following is a general overview of conventional and investigative treatments for stage II-III multiple myeloma. Cancer treatment may consist of chemotherapy, targeted therapy, high-dose therapy and stem cell transplant, or a combination of these treatment techniques. Combining two or more of these treatment techniques has become an important approach for increasing a patient’s chance of cure and prolonging survival.
In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment. Treatments that may be available through clinical trials are discussed in the section titled Strategies to Improve Treatment.
Circumstances unique to each patient’s situation influence which treatment or treatments are utilized. The potential benefits of combination treatment, participation in a clinical trial, or standard treatment must be carefully balanced with the potential risks. The information on this website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.
Planning Treatment for Multiple Myeloma
Before beginning treatment for multiple myeloma your physician may discuss with you the option of undergoing high-dose chemotherapy with an autologous stem cell transplant, which utilizes the patient’s own stem cells. Most of the clinical trials conducted over the past two decades have shown that patients who undergo autologous stem cell transplantation after they have achieved a remission with conventional chemotherapy are more likely to experience a prolonged time to disease progression compared to patients who undergo only conventional therapy.
It is important discuss the possibility of a future autologous stem cell transplant at the time of diagnosis because stem cells have to be collected and frozen early in the disease course even if the treatment plan involves reserving the transplant for treatment after the disease recurs.
The other reason it is important to have this discussion is that opting to plan for an autologous stem cell transplant determines which chemotherapy drugs will make up the initial treatment. Alkeran® (melphalan) damages stem cells making collection difficult or impossible. Thus, patients who elect to have stem cells collected and stored are frequently treated with a Thalomid® (thalidomide)-based regimen that does not include Alkeran. Patients who elect not to receive a stem cell transplant, or who are not candidates for stem cell transplantation because of advanced age or poor health, are often treated with an Alkeran-based regimen.
Standard-Dose Systemic Therapy for Multiple Myeloma
Most patients with stage II or III multiple myeloma will initially receive standard-dose chemotherapy. The main goal of initial treatment is to induce a complete or near complete disappearance of myeloma cells, and this treatment is sometimes referred to as induction therapy. The selection of initial therapy depends largely on patient age and general medical condition. Patients in good health irrespective of age are often treated aggressively to produce a complete remission while more debilitated patients receive less aggressive therapy at the beginning of treatment.
There are a large number of chemotherapy drugs approved by the US Food and Drug Administration for initial treatment of multiple myeloma, including the following:
- Alkeran® (melphalan)
- Adriamycin® (doxorubicin)
- Oncovin® (vincristine)
- Thalomid® (thalidomide)
- Cytoxan® (cyclophosphamide)
- Velcade® (bortezomib)
These agents are usually administered in combination with other drugs. Some of the common combinations include:
- Thalomid and dexamethasone
- MP (Alkeran and prednisone)
- MP plus Velcade
- MP plus Thalomid
- VAD (Oncovin, Adriamycin and dexamethasone)
- Cytoxan, Thalomid and dexamethasone
Thalomid-based therapy: Currently more than 70% of newly diagnosed patients receive a combination that includes Thalomid. Results of clinical trials indicate that combination treatment with Thalomid and dexamethasone produces anticancer responses in approximately two-thirds of patients, which is significantly improved over dexamethasone treatment alone.,
Alkeran-based therapy: Prior to the widespread use of Thalomid the most frequently used regimens were Alkeran and prednisone and Oncovin, Adriamycin and dexamethasone (VAD). Alkeran-based therapy is still the most common treatment for patients who do not plan to undergo autologous stem cell transplant at some point in their disease course.
Alkeran and prednisone has been shown to produce anticancer responses in more than half of patients (60%), and that response lasts for a year and a half, on average. Patients typically survive two to three years after treatment with Alkeran and prednisone. While patients may respond more quickly to combination chemotherapy such as VAD, overall, anticancer responses are the same with Alkeran and prednisone.
Alkeran, prednisone, and Velcade: A benefit of Velcade among patients with previously untreated multiple myeloma was demonstrated by the phase III VISTA trial. Study participants received treatment with either MP (Alkeran and prednisone) alone or MP plus Velcade. A complete response (complete disappearance of detectable myeloma) occurred in 30% of patients treated with MP plus Velcade, but only 4% of patients treated with MP alone. Patients treated with Velcade also had better progression-free survival.
Alkeran, prednisone, and Thalomid (MPT): The addition of Thalomid to Alkeran/prednisone appears to produce quick and lasting anticancer responses in the treatment of patients with newly diagnosed multiple myeloma. Clinical trial results indicate that patients responded to MPT treatment within four months and nearly three-quarters of patients experienced a partial or near-complete disappearance of their myeloma. Approximately nine out of 10 patients (91%) survived two years or more after treatment.
The addition of Thalomid to Alkeran/prednisone also appears to improve outcomes in the treatment of elderly patients compared to Alkeran/prednisone alone. More than three-quarters (76%) of patients treated with the three-drug combination experienced complete or partial remissions compared to less than half (47.6%) of patients treated with Alkeran/prednisone.
MPT also appears to produce longer survival compared to intermediate-dose Alkeran followed by autologous stem cell transplantation in the treatment of elderly patients with multiple myeloma.
High-dose Therapy and Stem Cell Transplant for Multiple Myeloma
High doses of chemotherapy are more effective at killing cancer cells than lower doses. However, high-dose therapy destroys many other cells in the body. A dangerous side effect of administering high-dose therapy is damage to the stem cells in the bone marrow that develop into mature blood cells. Without functioning stem cells in the bone marrow, the body cannot produce red blood cells, white blood cells or platelets, which leaves patients vulnerable to infection and bleeding, and unable to supply adequate oxygen to their tissues.
However, bone marrow function can be restored after high-dose therapy by replacing the damaged stem cells with healthy ones. This is a procedure known as a stem cell transplant.
There are two possible sources of stem cells for transplantation; they may be collected from the patient prior to undergoing high-dose therapy or they may be collected from a donor. A stem cell transplant that utilizes the patient’s own cells is called an autologous stem cell transplant. When the stem cells are from a donor the procedure is called an allogeneic stem cell transplant.
High-dose therapy followed by autologous stem cell transplant (ASCT) is a standard approach to treating patients with stage II or III multiple myeloma. Following an initial ASCT, some patients may benefit from a second ASCT. This is known as a tandem, or double, transplant. Studies have suggested that patients who do not achieve a complete or very good anti-cancer response to the first ASCT are the most likely to benefit from a second ASCT.
In general, autologous transplants are performed much more frequently than allogeneic transplants. This is due to the fact that there are relatively few patients with suitable donors and because allogeneic transplants are associated with more treatment-related complications. In an attempt to reduce treatment-related side effects which can be significant, some researchers have explored the role of reduced-intensity (RIC) allogeneic stem cell transplantation. This approach carries a lower risk than conventional allogeneic stem cell transplant, but has also been linked with a higher risk of relapse. Nevertheless, one small study has reported that ASCT followed by RIC allogeneic stem cell transplantation resulted in better overall survival than tandem ASCT.
Initial High-Dose Therapy and Stem Cell Transplant or Wait Until After Relapse?
ASCT is a treatment that is often reserved until multiple myeloma recurs after initial treatment or progresses with treatment. Results of clinical trials indicate that patients did not live longer if they opted for this treatment early in their disease course as opposed to waiting until their myeloma recurred.  Based on these findings, a recent review of multiple myeloma concluded that the timing of ASCT “is based on patient and physician preference and the ability to cryopreserve stem cells.”9 A potential advantage of early ASCT is that it involves a shorter duration of chemotherapy.
It is important to note that undergoing transplantation later in the treatment strategy is more likely to be successful if it is planned for. Stem cells must be collected prior to any other initial treatment because the bone marrow becomes damaged even with conventional-dose chemotherapy.
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Millennium Pharmaceuticals. FDA approves Velcade® (bortezomib) for injection for patients with previously untreated multiple myeloma. Available at: http://investor.millennium.com/phoenix.zhtml?c=80159&p=irol-newsmediaArticle&ID=1168334&highlight=. Accessed June 2008.
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 Fermand J-P, Ravaud P, Chevret S, et al. High-Dose Therapy and Autologous Peripheral Blood Stem Cell Transplantation: UP-Front or Rescue Treatments? Results of a Multicenter Sequential Randomized Trial. Blood. 1998;92:3131-3136.
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