Erythropoietin stimulation agents significantly improve outcome in lower-risk myelodysplastic syndrome

The large prospective EUMDS registry study demonstrates a significant survival advantage for lower-risk myelodysplastic syndrome (MDS) patients exposed to erythropoietin stimulation agents (ESA) at onset of anaemia but before onset of transfusion therapy, strongly supporting recommendations to start ESA treatment early. Moreover, ESA exposure is associated with maintained quality of life (QoL), while red blood cell transfusion dependency is associated with significant deterioration in QoL.

The EUMDS Registry started in 2008 as a prospective, non-interventional longitudinal study, enrolling newly diagnosed patients with IPSS low or intermediate-1 myelodysplastic syndrome (MDS) from 16 European countries and Israel. As it was not clear whether to start ESA before or after a transfusion need occurs, the aim of the present analysis was to see how treatment with or without erythropoietin stimulating agents (ESA) and/or red blood cell transfusions (RBCT) impact overall survival (OS) and quality of life (QoL).

Study design

Patient management was recorded electronically every 6 months (“visit”) in a central database, including treatment, transfusions, blood values, and health-related quality of life (HRQoL) using the EQ-5D 3-Level index and Visual Analog Scale (VAS). Patients were eligible to be included in the analyses if they had lower risk MDS, a haemoglobin (Hb) level <10 g/dl and when they were diagnosed before July 2019. To overcome potential confounding by non-random allocation of ESA treatment, propensity score matching was performed to ensure that treated and untreated patients had similar characteristics. Only patients with comparable propensity scores were included in the analyses to estimate the effects of ESA treatment on outcomes using standard time to event analyses. Overall survival was estimated from the first visit a Hb value of <10g/dl was recorded. OS was examined for patients treated with ESA stratified by their transfusion status prior to commencing ESA treatment (no RBCT, <4 units, ≥4 units).

Patients were separated into 4 groups at each clinical visit, depending on the treatment received in the interval leading up to that visit; no ESA nor RBCT, ESA only, ESA and RBCT and RBCT only. Health-related quality of life (HRQoL) at each visit according to the treatment status was summarised for patients who had completed a questionnaire at visit 1 and 2; mean values were examined by treatment group.

Results

Of 2,562 patients registered by November 2021, 2,448 were diagnosed before July 2019 and included in the analysis. These patients were divided into two groups: ESA untreated (N= 1,265) and ESA treated (N= 1,183). Patients whose Hb remained above 10 g/dl were excluded, leaving 529 untreated patients and 749 ESA treated. After propensity score matching was applied, two comparable groups were produced: ESA untreated (N=  426) and ESA treated (N= 742).

There was a clear OS advantage to the ESA-treated group, with a median OS of 44.9 months as compared to 34.8 months for the non-ESA group (p< 0.003). Of note, there was a poorer OS in patients transfused prior to commencing ESA (p< 0.001), with the worst OS for patients who received more than 4 RBC units before ESA treatment. Keyslide 3 shows the number of patients at each visit who had been treated with transfusions and/or ESA; 647/1,278 patients had received neither at visit 1. The Sankey diagram shows the “flow” of patients by treatment for the first 6 visits. HRQoL was examined for the 695 patients who had completed a questionnaire at both visit 1 and 2 up to visit 6. Differences in HRQoL were seen by treatment. Patients who had received neither ESA nor RBCT reported, on average, the highest mean HRQoL. In contrast, patients who had RBCT, either with or without ESA, had the lowest HRQoL (p<0.001).

Conclusion

ESA significantly improves outcome in lower-risk MDS and it is important to start ESA before a transfusion need occurs. Moreover, ESA exposure is associated with maintained QoL, while RBCT development with or without ESA exposure is associated with significantly deterioration in QoL.

Reference

Garelius H, et al. Erythropoietin stimulation agents significantly improves outcome in lower risk MDS. Presented at EHA 2022; Abstract S168.