Management of Anemia in Lymphoma Patients Treated with Erythropoiesis Stimulating Agents (ESAs): Findings from the European Anemia Cancer Treatment (A.C.T.) Study
Authors: Ludwig Heinz , Bokemeyer Carsten , Soubeyran Pierre , Aapro Matti , 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 lymphoma. 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 lymphoma.
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. 128 centers in 13 European countries contributed 324 multiple myeloma pts who were anemic (hemoglobin [Hb] 11g/dL) and treated with an ESA (14.8% 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 18 to 92 years (58.4±17.6). 96.1% of pts were on chemotherapy, of which 83.4% on standard vs. 16.6% on high dose; and 17.8% on platinum vs. 82.2% on nonplatinum. Types of ESA prescribed included epoetin alfa (13.0%), epoetin beta (43.5%), darbepoetin alfa (43.5%). Results are summarized in Table 1. No severe adverse events were reported.
Table 1
Treatment patterns and outcomes Visit 1 Visit 2 Visit 3 P Mean (SD) ESA dose (IU/week) 31851 (6912) 33844 (10296) 33610 (10199) 0.002 Median ESA dose (IU/week) 30000 30000 30000 n.s. Mean (SD) Hb (g/dL) 9.3 (1.0) 10.2 (1.4) 10.9 (1.7) &lt;0.001 WHO/ECOG performance status 1.04 (0.83) 0.98 (0.75) 0.90 (0.79) 0.002 % pts on iron 19.2% 18.1% 15.2% n.s. % pts on iron who are on IV iron 16.4% 23.3% 20.0% n.s. % pts with ESA dose escalation 8.4% 2.5% n.s. Response rates Hb↑≥1g/dL Hb↑≥1g/dL within 8wks Hematopoietic response Hb↑≥2g/dL 12–12.9g/dL % pts 67.9% 60.8% 44.4% 39.8% 20.7%
CONCLUSIONS. The slight increase in ESA dose was not in accordance with the stable median ESA dose across the three visits. 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 two-thirds of lymphoma 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 lymphoma 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.