Prospective Targeted Epoietin beta Therapy for Chemotherapy-Associated Anaemia Achieves High Response Rates.
Authors: Agrawal Samir G. , Lim Christina , Cavill Ivor 
Published: April 2020

Background: EPO for management of chemotherapy-associated anaemia in patients with cancer is recommended by international guidelines. However, the variable response rate to EPO limits its effective deployment. In the UK, a ‘predictive factor testing service (PFTS)’ (supported by Roche) ascribes a low, moderate or high probability of response to EPO therapy - based on a two step holostic evaluation: (i) the state of erythropoiesis (serum EPO in relation to Haemoglobin concentration [Hb]; reticulocyte count and %); (ii) the need for IV iron to support erythropoiesis (MCH, reticulocyte Hb and serum ferritin).

Aims: To assess the utility of the PFTS and iron supplementation in improving response rates to EPO used for chemotherapy-induced anaemia.

Patients and methods: an ASH/ASCO based-guideline for EPO therapy was developed. The criteria were: patients with CLL, myeloma and NHL (excluding diffuse large B-cell NHL); Hb &lt; 10 g/dl; on chemotherapy; a moderate or high PFTS score. EPO dose: 30,000 units s.c. once weekly, increased to 60,000 at 4 weeks if there was no response (NR: Hb increase of &lt; 1g/dl over baseline). EPO was stopped at 8 weeks if NR. Minor (MiR) and major (MaR) responses were defined as: Hb increase of 1 - 2 and &gt; 2 g/dl, respectively. Iron dose: iron sucrose (Venofer) 200mg IV weekly for 3 doses, repeated as indicated. Two successive 6-month, prospective audits (I and II) were performed, which differed only in that audit II, in addition to the PFTS score, also took into account the recommendation for IV iron supplementation. We retrospectively audited a 6-month period preceding the guideline introduction and analysed Hb response and red blood cell transfusion (RBC TX) of those patients who would have been eligible for EPO.

Results: Prospective audit (I) - 12 patients received EPO; 8 (66%) responded. Hb levels and RBC Tx are shown in table 1. Prospective audit (II) - 25 patients qualified for EPO; 23 patients (92%) responded, with 17 MaR. Hb levels and RBC Tx are shown in table 1. Iron supplementation: Nine patients received IV iron. Seven patients received IV iron from week 0 and all responded; one patient from week 4, who converted from NR to MaR; and one patient received IV iron at week 8, but failed to maintain a MiR. Thus, 8/9 patients given IV iron responded (7 MaR) and 5 had EPO dose reductions. EPO dosage: Overall, there was a dose reduction of EPO in 8 patients, and a dose increase in 4 (2 responses achieved). The average EPO dose was 340,000 units/patient.

The 6-month retrospective audit data is also shown in table 1.

Conclusion: an holistic approach, using readily available laboratory parameters, to assess erythropoietic status and the need for IV iron supplementation has increased the response rate to EPO from 66 to 92%. The limited data presented here suggests similar response rates can be achieved in cancer as in renal use of EPO. This approach to targeted EPO therapy warrants further investigation and validation.

Hb and RBC Tx outcomes both with and without EPO Patients (n) Mean Hb weeks 0 /4 /8 /12 Responders Mean Hb weeks 0 /4 /8 Non responders Total RBC Tx (units /patient) #: patients who would have been eligible for EPO ; *: mean Hb at each visit; Retro. Audit: retrospective audit ; Prosp. Audit: prospective audit; R: responders ; NR: non responders Retro. Audit 17# 8.0* 5.5 Prosp. Audit - I (R) 8 8.6 /10.3 /− /− 1.1 Prosp. Audit – I (NR) 4 8.9 /8.3 /− 6.0 Prosp. Audit – II (R) 23 9.5 /10.5 /11.6 /11.8 0.8 Prosp. Audit – II (NR) 2 8.9 /8.6 /7.6 4.5