A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-α in anemic patients with low-risk MDS

Abstract

Erythropoiesis-stimulating agents are first choice for treating anemia in low-risk MDS. This double-blind, placebo-controlled study assessed the efficacy and safety of epoetin-α in IPSS low- or intermediate-1 risk (i.e., low-risk) MDS patients with Hb ≤ 10.0 g/dL, with no or moderate RBC transfusion dependence (≤4 RBC units/8 weeks). Patients were randomized, 2:1, to receive epoetin-α 450 IU/kg/week or placebo for 24 weeks, followed by treatment extension in responders. The primary endpoint was erythroid response (ER) through Week 24. Dose adjustments were driven by weekly Hb-levels and included increases, and dose reductions/discontinuation if Hb > 12 g/dL. An independent Response Review Committee (RRC) blindly reviewed all responses, applying IWG-2006 criteria but also considering dose adjustments, drug interruptions and longer periods of observation.A total of 130 patients were randomized (85 to epoetin-α and 45 to placebo). The ER by IWG-2006 criteria was 31.8% for epoetin-α vs 4.4% for placebo (p < 0.001); after RRC review, the ER was 45.9 vs 4.4% (p < 0.001), respectively. Epoetin-α reduced RBC transfusions and increased the time-to-first-transfusion compared with placebo.Thus, epoetin-α significantly improved anemia outcomes in low-risk MDS. IWG-2006 criteria for ER may require amendments to better apply to clinical studies.

Effects of erythropoiesis-stimulating agents on overall survival of International Prognostic Scoring System Low/Intermediate-1 risk, transfusion-independent myelodysplastic syndrome patients: a cohort study

“…Effects of erythropoiesis-stimulating agents on overall survival of IPSS low/INT-1 risk, transfusion independent myelodysplastic syndrome patients: a cohort study Clinical guidelines recommend the use of erythropoietin stimulating agents (ESAs) in lower risk anaemic myelodisplastic syndrome (MDS) patients [1][2][3][4] and two registration trials for ESAs have just been completed 5,6 . We conducted a retrospective study in MDS patients selected by the characteristics predictive of ESA response 7 , treated in common practice and enrolled in the Italian Network of regional MDS registries (ClinicalTrials.gov Identifier: NCT02808858)…”

Clinical effectiveness and safety of erythropoietin‐stimulating agents for the treatment of low‐ and intermediate‐1−risk myelodysplastic syndrome: a systematic literature review

“…The source files for the EPOANE3021 study used in the analysis included an online clinical study report (Janssen‐Cilag International N.V., ) and a published abstract (Fenaux et al , ). The EPOANE study was published after the analysis was conducted; therefore, that citation (Fenaux et al , ) was cited in the paper.…”

“…Similar results were observed in RCTs of short‐acting ESAs. In the EPOANE3021 study, the percentage of patients who required transfusions in the epoetin alfa group steadily declined, from 51·8% in the 8 weeks prior to baseline to 24·7% of patients between weeks 16 and 24, and was essentially unchanged in the placebo group (from 48·8% to 54·1%, respectively) (Fenaux et al , ). In another study, 29% of patients who received epoetin alfa plus standard care were still receiving transfusions at 4 months compared with 51% of patients who received standard care alone (Greenberg et al , ).…”

“…All RCTs of short‐acting ESAs reported rates of progression to AML. For those studies that compared epoetin alfa with placebo, rates of AML progression ranged from 2·6% to 3·5% for epoetin alfa and from 2·7% to 4·4% for placebo (Ferrini et al , ; Fenaux et al , ). Identical rates for AML progression were reported for erythropoietin alfa compared with erythropoietin alfa in combination with G‐CSF (13·3%) (Balleari et al , ).…”

“…This lack of difference may have been due to the fact that haemoglobin levels were not allowed to decrease in the placebo arm (patients received RBC transfusions when haemoglobin decreased to ≤80 g/l) to an extent that impacted QoL. In a post‐hoc analysis of the EPOANE3021 study, significant improvement in QoL scores were observed at week 24 with epoetin alfa treatment in responders compared with non‐responders (FACT‐Anaemia, EQ‐5D, and EQ‐visual analogue scale), but the magnitude of the effect was not reported, so the results cannot be clinically interpreted (Fenaux et al , ).…”