New Biologic Therapy, Using Dendritic Cells, Produces Responses with Myeloma

New Biologic Therapy, Using Dendritic Cells, Produces Responses in Persons with Low-Burden Multiple Myeloma

A newly developed type of biologic therapy, or immunotherapy, has produced responses in some persons with multiple myeloma. The infusion of dendritic cells, cells in the blood that process antigens, has resulted in the remission of disease in persons who have low-burden multiple myeloma, according to a report presented at the recent American Society of Clinical Oncology meeting in New Orleans.

Multiple myeloma, a type of cancer called a plasma cell neoplasm, is characterized by the presence of cancerous plasma cells in multiple sites in the body, but particularly in the bone marrow. The bone marrow (and circulating blood) contains early blood-forming cells, called stem cells, which grow and mature into the 3 blood cell types: white blood cells (protect the body from infection), red blood cells (carry oxygen to the tissues), and platelets (help the blood to clot). The plasma cells are produced by a type of white blood cell, called a lymphocyte, and serve to protect the body from infection. The cancerous plasma cells can crowd out other cells, such as red blood cells; can cause a breakdown of bone; and can collect to form tumors (called plasmacytomas) in the bone. The cancer cells produce an abnormal protein, a monoclonal immunoglobulin (or antibody), often referred to as an M-protein. Parts of the M-protein can be detected in the blood and urine of persons with multiple myeloma, and measurements of the M-protein can then be used to monitor the status of the cancer.

Once the symptoms of disease manifest, persons with multiple myeloma are usually treated with chemotherapy. They may initially receive chemotherapy drugs at the standard doses, sometimes followed by chemotherapy drugs given in high doses with a stem cell transplantation. However, persons with multiple myeloma might instead receive the high-dose chemotherapy with a stem cell transplant initially, as this approach has resulted in improved survival. High doses of chemotherapy kill more cancer cells than standard doses, but also destroy more of the stem cells in the bone marrow.

A stem cell transplantation is a procedure that allows the stem cells that are damaged or destroyed by high-dose chemotherapy to be replaced with healthier stem cells. In the case of an autologous stem cell transplantation, stem cells are collected from the blood or bone marrow of the patient before receiving high-dose chemotherapy, are frozen, and then infused back into the patient after he or she has undergone the high-dose therapy. This procedure replaces the stem cells that have been destroyed by the high-dose chemotherapy, thereby allowing more rapid recovery and production of the red blood cells, white blood cells, and platelets that the body needs. In many cases, the stem cells are collected from the patients blood after he or she receives initial standard-dose chemotherapy and a biologic therapy, called a growth factor (or the growth factor alone). If collection of the stem cells is performed early in the standard-dose chemotherapy treatment course, enough stem cells can often be harvested to support several courses of high-dose chemotherapy later. However, if this procedure is delayed until a large amount of chemotherapy has been given, it may no longer be possible to collect enough stem cells to restore the bone marrow after high-dose therapy.

Even when high-dose chemotherapy is given as an initial treatment, many persons will have small amounts of cancer cells, or minimal residual disease, left in the blood and bone marrow. This residual disease may grow and result in a recurrence (return or relapse) of the multiple myeloma later. Researchers are now working to develop biologic therapies that will help prevent a recurrence of multiple myeloma by eradicating the cancer cells that are left after high-dose chemotherapy.

Researchers at the Mayo Clinic have developed a new type of biologic therapy, using dendritic cells, cells in the blood that process antigens. The dendritic cells, loaded with a myeloma antigen, are infused into the patient in an effort to stimulate the bodys immune system to attack the myeloma antigen and consequently also attack the cancerous myeloma cells. The researchers treated patients with a high level of detectable M-protein (called high-burden multiple myeloma) as well as those with a low level of detectable M-protein (called low-burden multiple myeloma). Most of the patients with low-burden multiple myeloma had undergone high-dose chemotherapy with an autologous stem cell transplant. All patients were treated with an infusion of dendritic cells. The results showed that 3 of 13 patients with low-burden multiple myeloma had complete eradication of myeloma cells, and 3 others had a partial clearing of the myeloma cells. Only 1 of the 13 patients experienced progression of the cancer after the therapy. In patients with high-burden multiple myeloma, no patient had a complete or partial response to the therapy; however, the time it took for the disease to progress appeared to be prolonged.

These findings suggest that the use of biologic therapy with dendritic cells, loaded with the myeloma antigen, appears to produce complete responses in some persons with low-burden multiple myeloma, including those who have previously undergone chemotherapy and an autologous stem cell transplant. Individuals who have this type of disease may wish to talk with their doctor about the risks and benefits of participating in a clinical trial in which dendritic cell therapy or other promising new treatment approaches are being studied. (Proceedings of the American Society of Clinical Oncology Thirty-Sixth Annual Meeting, Vol 19, Abstract 1776, p 453a, 2000)

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