High-Dose Chemotherapy Improves Survival as Initial Therapy in Multiple Myeloma

High-Dose Chemotherapy Improves Survival as Initial Therapy in Multiple Myeloma

According to a recent article published in the The New England Journal of Medicine, high-dose chemotherapy with an autologous stem cell transplant improves survival over conventional doses of therapy as initial treatment of multiple myeloma.

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 patients 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.

The use of high-dose chemotherapy and stem cell transplantation has remained controversial in the treatment of multiple myeloma. Although anti-cancer response rates have been demonstrated to be superior with high-dose therapy versus conventional doses, data is limited regarding overall survival benefits.

Researchers from Medical Research Council Adult Leukaemia Working Party recently conducted a clinical trial directly comparing high-dose chemotherapy and autologous stem cell transplantation to conventional standard therapy as initial treatment of multiple myeloma. This trial involved approximately 400 patients under the age of 65; half of whom were randomly selected to be treated with the high-dose regimen and half of whom were randomly selected to be treated with conventional doses. Complete anti-cancer responses occurred in 40% of patients treated with the high-dose regimen, compard to only 8% treated with standard doses. Overall survival was improved by almost one year in the group of patients treated with high-dose therapy (54.1 months), compared to the group treated with conventional doses (42.3 months). Patients with a poor prognosis as indicated by high levels of beta2-microglobulin levels tended to gain the most survival benefit from high-dose therapy.

These results indicate that high-dose chemotherapy with autologous stem cell transplantation appears to improve survival over conventional doses as initial therapy for patients with multiple myeloma under the age of 65. Patients with multiple myeloma may wish to discuss the risks and benefits of high-dose therapy and stem cell transplantation with their physician.

Reference: Child J, Morgan G, Davies F, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma.

The New England Journal of Medicine. 2003;348:1875-1883.

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