Development, Prediction, and Treatment of Anemia in Patients (pts) with Lymphoma/Multiple Myeloma (L/M): Findings of Two European Surveys (ECAS and BEPOS).
Authors: Ludwig Heinz , Van Belle Simon , Gascón Pere 
Published: April 2020

Abstract
Quality of life (QOL) in cancer pts is adversely affected by several factors, including disease- or treatment-related anemia. Between January 2001 and February 2002, the European Cancer Anaemia Survey (ECAS) was conducted to provide information on pervasiveness of cancer-related anemia, impact of anemia on WHO performance status, risk factors for its development, and anemia treatment practices in Europe. Briefly, a total of 15,370 pts were enrolled, of whom 2,360 had L/M. Data analysis showed 53% of L/M pts were anemic (hemoglobin [Hb] &lt;12 g/dL) at enrollment and 73% were anemic at some time during the survey. Low Hb levels correlated significantly with WHO performance scores of 3 or 4 (P &lt;0.001, R =.352). The ECAS data were additionally analyzed to determine patient and disease characteristics that predicted anemia development and to construct a model for identifying pts at risk. Using logistic regression on the L/M incidence group (pts who were not anemic and not being treated for cancer at enrollment, started chemotherapy [CT] during ECAS, and had at least 2 CT cycles during the survey), 4 variables were found to significantly predict anemia development. Initial Hb, persistent/recurrent disease, female gender, and intent to treat or treatment with platinum-based CT were found to independently predict anemia (P &lt;0.001), with an area under the ROC curve of 0.821 (95% CI; 0.763–0.878), indicating acceptable predictive accuracy of the model. Three levels of risk (low [24%], moderate [51%], and high [72%]) for developing anemia were calculated from the model (χ2(2) = 112.6, P &lt;0.001). Mean time required for anemia development was 9.0 wks to reach Hb of &lt;12 g/dL, 11.1 wks to reach Hb of &lt;11 g/dL, and 13.3 wks to reach Hb of &lt;10 g/dL. Notably, only 46% of anemic L/M pts received anemia treatment. Subsequently, a recent (2003) survey, the Belgian Erythropoietin Survey (BEPOS), extended the information gained through ECAS by examining use of recombinant human erythropoietin (rHuEPO) in pts receiving CT. Specifically, BEPOS documented when rHuEPO treatment was started, dosing schedules and dosage adjustments, length of treatment, impact of iron supplementation on rHuEPO treatment, and outcomes. Patients enrolled had either solid tumors (non-small-cell lung cancer, breast cancer) or hematologic malignancies (multiple myeloma [MM], Hodgkin’s disease [HD], non-Hodgkin’s lymphoma [NHL]). Interim results suggest that 72% of BEPOS pts began rHuEPO during the first 2 CT cycles, with an overall median Hb value of 10.1 g/dL at treatment initiation. For hematologic malignancy pts, the median Hb at treatment initiation was ~10 g/dL for HD; in NHL and MM, the median Hb was &gt;9 to &lt;10 g/dL. Mean time for all pts to achieve a 2-g/dL increase in Hb in the absence of transfusion was 6.4 wks; mean time for NHL pts (6.3 wks) was similar, while mean time for MM pts (9.1 wks) was longer, more in line with that seen in clinical trials. Achievement of the 2-g/dL increase in Hb after 6.4 wks determined in BEPOS is consistent with increases of ~1 g/dL after 4 wks and ~2 g/dL after 8 wks noted in studies of epoetin alfa (Demetri 1998, Gabrilove 2001, Littlewood 2001). Using the large ECAS database, an anemia risk model has been established that should help identify pts at risk for anemia, so that administration of rHuEPO can be initiated expeditiously, before Hb declines to considerably lower levels and/or anemia symptoms, including impaired QOL, develop.