According to results recently published in The New England Journal of Medicine, two autologous stem cell transplants appear to improve long-term survival over a single autologous stem cell transplant in patients with untreated multiple myeloma under the age of 65.
1 The results from this trial were also presented at the 2002 annual meeting of the American Society of Hematology.
Multiple myeloma is a cancer involving important immune (infection-fighting) cells called plasma cells. Plasma cells aid the body in fighting infection by producing specialized proteins called antibodies that have the ability to target and/or kill foreign cells. In multiple myeloma, cancerous plasma cells produce abnormal and excessive antibodies that do not have the ability to properly fight infection. In addition, the cancerous plasma cells accumulate in the bone marrow, suppressing the normal formation and function of other cells that are necessary for normal production of blood cells and immune functions. The excessive accumulation of cancer cells in the bone marrow ultimately leads to the formation of tumors in the bone and to the breakdown of bone. Standard treatment for multiple myeloma is chemotherapy with or without stem cell transplant.
High-dose therapy (chemotherapy and/or radiation) kills more cancer cells than moderate doses. However, more healthy cells, including stem cells, are also killed due to the high doses, often causing significant side effects. Stem cells are immature blood cells produced in the bone marrow that mature into red blood cells, which carry oxygen to tissues; white blood cells, which fight infection; and platelets, which aid the blood in clotting. Autologous stem cell transplants involve the collection of patient’s stem cells prior to treatment and re-infusion following high-dose therapy to restore depleted blood cell levels. The high doses of therapy are often difficult for patients to tolerate, particularly the elderly. Thus, physicians often reserve high-dose therapy and stem cell transplantation for patients under the age of 65 years. Prior to high-dose therapy, patients are treated with moderate doses of chemotherapy, called “induction therapy”.
Although some clinical results have indicated that two autologous stem cell transplants appear to improve survival over a single autologous stem cell transplant in patients with multiple myeloma, the first clinical trial directly comparing these two treatment strategies has only recently been conducted. This trial was conducted by a French consortium of 36 medical centers and involved 339 patients with newly diagnosed multiple myeloma who received either a single autologous transplant or a double autologous stem cell transplant. The single transplant patients were treated with high-dose melphalan and total body irradiation followed by stem cell transplantation. The double transplant patients were treated with high-dose melphalan and autologous stem cells followed by high-dose melphalan and total body irradiation and an additional autologous stem cell infusion. The induction therapy for all patients was a chemotherapy regimen referred to as VAD (vincristine, Adriamycin® and dexamethasone).
Seven years following therapy, progression-free survival was 21% following double stem cell transplants, compared to only 10% following a single transplant. Overall survival was 42% for patients treated with a double transplant, compared to only 21% for those treated with a single transplant. Patients who had less than a 50% reduction in cancer following induction therapy or the first transplant benefited the most from a second transplant. Patients who had at least a 50% anti-cancer response to induction therapy or the first transplant did not appear to benefit from a second transplant. Seventy-eight percent of patients treated with double transplants were able to complete treatment, compared to 82% of patients treated with a single transplant.
These authors concluded that patients with newly diagnosed multiple myeloma under the age of 65 years who do not achieve at least a 50% reduction in cancer following induction therapy with VAD or a first autologous stem cell transplant appear to achieve significant long-term survival benefit from a second autologous transplant. Patients with multiple myeloma under the age of 65 who have not responded well to either induction therapy or a first autologous transplant may wish to speak with their physician about the risks and benefits of participating in a clinical trial further evaluating a double transplant.
1.Attal M, Haroussear J-L, Facon t, et al. Single Versus Double Autologous Transplantation for Multiple Myeloma.
The New England Journal of Medicine. 2003;349:2495-2502.
2.Attal M, Haroussear J-L, Facon T, et al. Double autologous transplantation improves survival of multiple myeloma patients: final analysis of a prospective randomized study of the “Intergroupe Francophone du Myelome” (IFM). Proceedings from the 2002 annual meeting of the American Society of Hematology.
Blood. 2002;1005a: abstract #7.