A group of leading myeloma specialists, known as the International Myeloma Working Group, recently collaborated to develop guidelines for the proper management of anemia with erythropoietin therapy in multiple myeloma patients. The group advised erythropoietin therapy for anemic myeloma patients receiving chemotherapy in order to improve quality of life and to reduce the need for red blood cell transfusions. They further recommended the addition of iron to improve the efficiency of erythropoietin therapy.

Dr. Heinz Ludwig of the Wilhelminen Hospital in Vienna, Austria, presented these guidelines at the International Myeloma Workshop (IMW) on May 6 in Paris.

Anemia, a condition caused by a low number of healthy red blood cells, is a common complication of multiple myeloma that can cause fatigue, chest pain, dizziness, headaches, shortness of breath, and problems concentrating. It is estimated that 30 percent to 60 percent of myeloma patients have anemia at the time of diagnosis, and up to 90 percent of elderly patients develop anemia throughout the course of therapy.

Erythropoietin is a hormone secreted by the kidneys that stimulates the bone marrow to produce red blood cells. Erythropoiesis-stimulating agents, which are man-made versions of erythropoietin that are available as prescription medications, can be given to anemic myeloma patients to increase red blood cell production.

Before treating a myeloma patient for anemia, the guidelines say the physician must identify the cause of the anemia. For instance, anemia can be caused by chemotherapy, the cancer itself, or non-myeloma-related causes, such as severe infection, blood loss, or the premature destruction of red blood cells. Erythropoietin therapy is approved only for cancer patients receiving chemotherapy, although myeloma patients with severe anemia caused by chronic disease may be considered for therapy after discussion with their physicians.

For anemic myeloma patients receiving chemotherapy, the guidelines recommend the initiation of erythropoietin therapy once the patient’s hemoglobin levels drop to 10 g/dl, or at higher hemoglobin levels if the patient experiences symptoms of anemia. These patients should receive 40,000 U once per week or 10,000 U three times per week. Patients receiving erythropoietin therapy in the form of Aranesp (darbepoetin alfa) should receive a dose of 150 µg per week or 500 µg every three weeks.

The guidelines suggest the continuation of therapy until hemoglobin levels reach 12 g/dl.  If levels drop after discontinuation, therapy should be resumed once hemoglobin levels reach 10 g/dl or when symptoms occur.

For patients who do not respond to erythropoietin therapy, there is little evidence that supports the effectiveness of dose increases.  Therefore, patients who do not respond to treatment within six to eight weeks should discontinue therapy.

In addition, the administration of intravenous iron has been shown to increase response rates to erythropoietin therapy for patients with chemotherapy-induced anemia. Because long-term statistics are not available, however, the recommendation for iron supplementation is standard only for patients with depleted iron stores and very low amounts of iron in the body.

A possible side effect of erythropoietin therapy is blood clots in the veins. Studies have also shown that patients receiving erythropoietin therapy without chemotherapy may have an increased risk for disease progression or death.

The guidelines advised measuring the level of iron bound to the protein transferrin in the blood (TSAT) as the most reliable test for identifying iron deficiency.  In addition, they recommended monitoring of hemoglobin levels, average amount of hemoglobin per red blood cell, average red blood cell size, levels of the protein ferritin, and the amount of iron in the blood during erythropoietin therapy.

For more information, please see the full guidelines (pdf), which are available on the IMW website.