The implications of anemia in multiple myeloma.

Multiple myeloma (MM) is commonly associated with anemia. Several causes have been implicated, but anemia of chronic disease with inadequate erythropoietin (EPO) production related to the inflammatory cytokines appears to be of utmost importance. Interleukin-1 and tumor necrosis factor are capable of suppressing erythropoiesis. Anemia has broad implications. First, the low hemoglobin and hematocrit are associated with poor quality of life and performance and affect daily activity. Second, anemia has an impact on the cardiovascular system. Considering that most MM patients are elderly, this may be even more important. Anemia has been shown to induce or aggravate hypoxia and ischemic complications. Third, anemia has been shown to be a poor prognostic factor in MM. Traditionally, patients with symptomatic anemia were treated with red blood cell transfusions as needed. The introduction of epoetin alfa and epoetin beta into clinical practice opened new avenues to these patients. The administration of epoetins to patients with MM and anemia have been shown to be very useful. Several studies in more than 1000 patients have demonstrated a high response rate (range, 25%-85%; mean, 60%). This response is characterized by a significant increase of hemoglobin, hematocrit, and the number of red blood cells together with a reduction in the blood transfusion requirements. This is also associated with an improved quality of life. Although there is no complete agreement about the role of pretreatment serum EPO levels, many investigators believe that relatively low levels may help in predicting response, thereby limiting the number of potential candidates to receive this expensive therapy. The epoetins are safe and well tolerated with minimal toxicity; however, some concern has been recently raised regarding several dozen patients who developed pure red cell aplasia while on epoetin therapy. However, this adverse effect appears to be extremely rare. Recent data suggest that EPO has additional biologic effects, such as longer-than-expected survival in patients with MM. This observation is further supported by animal studies, demonstrating an antimyeloma effect of EPO in mice models. This effect has been shown to be immune mediated. If these exciting data are confirmed in future clinical trials, this may have significant implications on the treatment of MM.