Management of Anemia in Multiple Myeloma Patients Treated with Erythropoiesis Stimulating Agents (ESAs): Findings from the European Anemia Cancer Treatment (A.C.T.) Study
Authors: Ludwig Heinz , Aapro Matti , Bokemeyer Carsten , Soubeyran Pierre , Muenzberg Michael , Turner Matthew , MacDonald Karen , Albrecht Tara , Abraham Ivo 
Published: April 2020

Abstract
BACKGROUND. The A.C.T. study has shown that in Europe more cancer patients (pts) with anemia are being treated with ESAs than 7 years ago. ESAs are indicated for multiple myeloma. Variability in treatment patterns, outcomes, and response rates in daily clinical practice need to be further investigated.
OBJECTIVE. To examine anemia treatment patterns, outcomes, and response rates in the subsample of A.C.T. patients with multiple myeloma.
DESIGN & PATIENTS. Multicenter, longitudinal retrospective study with at least 3 time points at approximately 1 month intervals, with visit 1 coinciding with start of ESA treatment. 111 centers in 10 European countries contributed 306 multiple myeloma pts who were anemic (hemoglobin [Hb] ≤11g/dL) and treated with an ESA (14.0% of total European sample).
MEASUREMENTS. All data collected through retrospective chart review. Key variables reported here: age, chemotherapy regimen, Hb, WHO/ECOG performance status, ESA type, ESA dose incl. escalation, and iron supplementation. Response to ESA Rx: Hb rise ≥1g/dL, Hb rise ≥1g/dL within 8 weeks, hematopoietic response (Hb rise ≥2g/dL or Hb≥12g/dL achieved), Hb rise ≥2g/dL, and Hb target range of 12.0–12.9g/dL achieved by visit 3.
RESULTS. Pts ranged in age from 26 to 91 years (66.6 11.0). 92.5% of pts were on chemotherapy, of which 94.6% on standard vs. 5.4% on high dose; and 6.7% on platinum vs. 93.3% on nonplatinum. Types of ESA prescribed included epoetin alfa (16.0%), epoetin beta (46.1%), darbepoetin alfa (37.9%). Results are summarized in Table 1. No severe adverse events were reported.
Table 1.
Treatment patterns & outcomes Visit 1 Visit 2 Visit 3 p Mean (SD) ESA dose (IU/wk) 30237 (7509) 30676 (8012) 30760 (8698) n.s. Median ESA dose (IU/wk) 30000 30000 30000 n.s. Mean (SD) Hb (g/dl) 9.2 (1.0) 10.3 (1.5) 11.0 (1.7) &lt;0.001 WHO/ECOG (SD) performance status 1.17 (0.84) 0.87 (0.66) 0.86 (0.73) &lt;0.001 % pts on iron 13.7% 9.2% 7.8% n.s. % pts on iron who are on IV iron 36.6% 46.4% 45.8% n.s. % pts with ESA dose escalation 4.4% 2.5% n.s. Response Rates Hb↑≥ 1g/dl Hb↑≥1g/dl within 8wks Hematopoietic response Hb↑≥ 2g/dl 12– 12.9g/dl % pts 72.2% 68.5% 50.7% 47.1% 21.6%
CONCLUSIONS. Mean and median dose did not change over time. Hb increased from visit 1 from visit 3 with a concomitant rise in performance status. Iron supplementation with, in particular, IV iron was consistently low. Dose escalation rates were low, perhaps reflecting that this be an individualized patient decision. An increase in Hb of ≥1g/dL over the course of treatment is an attainable goal in almost three-quarters of multiple myeloma pts with anemia. Adding time constraints, increasing the threshold level to ≥ 2g/dL, and/or setting an evidence-based target range of 12–12.9g/dL is associated with lower response rates. In multiple myeloma pts, the therapeutic Hb goal to be achieved may need to be determined under consideration of multiple factors, however the general effectiveness of ESAs in this population is evident.