Holmium 166 a Promising Component of High-Dose Therapy in Multiple Myeloma

Holmium 166 a Promising Component of High-Dose Therapy in Multiple Myeloma.

According to a recent article published in the journal Blood, the agent Holmium 166 may be an effective addition to high-dose chemotherapy and autologous stem cell transplantation in patients with relapsed 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 (spongy material inside large bones), 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. Furthermore, the cancerous plasma cells secrete dysfunctional antibodies, referred to as M proteins, which can be measured in the blood. Multiple myeloma that has progressed or returned following prior therapy is referred to as “recurrent”.

Patients with recurrent multiple myeloma may be eligible for treatment with a stem cell transplant, in which high doses of chemotherapy are used. The high doses of therapy tend to kill more cancer cells than conventional doses; however, the high doses also tend to kill more healthy cells. Stem cells, or immature blood cells, which include white blood cells, red blood cells and platelets, are particularly susceptible to high-dose therapy. Low levels of blood cells can lead to potentially life-threatening complications, so stem cells are collected from the patient prior to high-dose therapy, frozen and re-infused into the patient following therapy. This procedure is referred to as an autologous stem cell transplant and is used to restore levels of blood cells. In some cancers, total body irradiation may also be used in addition to, or in place of, high-dose chemotherapy. However, results from clinical trials demonstrated that the addition of total body irradiation does not improve outcomes compared to high-dose chemotherapy alone in the treatment of multiple myeloma. Total body irradiation is associated with significant side effects and researchers are evaluating ways to more specifically target cancer cells while sparing healthy tissue in order to reduce side effects caused by high-dose chemotherapy or total body irradiation.

Holmium 166 is an agent that is referred to as skeletal radiation therapy (SRT). It is a compound that seeks out and attaches to bone, delivering local radiation therapy. Since Holmium 166 delivers radiation therapy directly to bone and bone marrow, it spares surrounding organs and tissues from side effects of treatment. A request for initiation of the final phase of clinical trials has been submitted to the FDA for Holmium 166 in the treatment of multiple myeloma as an addition to high-dose chemotherapy with an autologous stem cell transplant.

Researchers from the MD Anderson Cancer Center, the Fred Hutchinson Cancer Center and the University of Miami recently presented results from two clinical trials evaluating treatment with Holmium 166 in patients with multiple myeloma. These trials included 82 patients, with an average of 2 previous therapies. Patients were treated with four regimens consisting of high-dose melphalan and Holmium 166 with differing doses followed by an autologous stem cell transplant. One group of patients also received radiation therapy. Anti-cancer responses were achieved in 65% of patients, with 35% achieving a complete disappearance of detectable cancer (complete response). The minimum duration of follow-up for these patients at the time of publication of this trial was 23 months, with the average duration of survival not yet reached. Side effects to the kidney were the dose-limiting side effect; however, this treatment regimen was generally well tolerated.

The researchers concluded that the addition of Holmium 166 to high-dose melphalan prior to autologous stem cell infusion appears promising. Results from future clinical trials directly comparing high-dose melphalan and autologous stem cell transplantation with or without Holmium 166 will provide insight to the true clinical utility of Holmium 166. Patients with multiple myeloma who are to undergo autologous stem cell transplantation may wish to speak with their physician regarding the risks and benefits of participating in a clinical trial further evaluating Holmium 166 or other promising therapeutic approaches.

Reference: Giralat S, Bensinger W, Goodman M, et al. 166Ho-DOTMP plus melphalan followed by peripheral blood stem cell transplantation in patients with multiple myeloma: results of two phase 1-2 trials.

Blood. 2003;102:2684-2691.

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