RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY EVALUATING EPOETIN ALFA VERSUS PLACEBO IN ANEMIC PATIENTS WITH IPSS LOW- INT1 RISK MDS
Author(s): ,
Pierre Fenaux
Affiliations:
Hôpital St Louis,Paris,France
,
Valeria Santini
Affiliations:
Hematology Unit-AOU Careggi,Florence,Italy
,
Maria Antonietta Aloe Spiriti
Affiliations:
Sapienza Università di Roma,Rome,Italy
,
Aristoteles Giagounidis
Affiliations:
Marien Hospital,Dusseldorf,Germany
,
Rudolf Schlag
Affiliations:
Praxisklinik Würzburg,Würzburg,Germany
,
Atanas Radinoff
Affiliations:
Tokuda Hospital Sofia,Sofia,Bulgaria
,
Liana Gercheva-Kyuchukova
Affiliations:
Varna Clinic of Haematology,Varna,Bulgaria
,
Achilles Anagnostopoulos
Affiliations:
George Papanicolaou Hospital,Thessaloniki,Greece
,
Esther Oliva
Affiliations:
Azienda Ospedaliera 'Bianchi-Melacrino-Morelli,Calabria,Italy
,
Argiris Symeonidis
Affiliations:
University of Patras,Patras,Greece
,
Anna Potamianou
Affiliations:
Janssen, Pharmaceutical Companies of Johnson & Johnson,Beerse,Belgium
,
Hari Haralampiev
Affiliations:
Janssen, Pharmaceutical Companies of Johnson & Johnson,Beerse,Belgium
,
Robert Wapenaar
Affiliations:
Janssen, Pharmaceutical Companies of Johnson & Johnson,Beerse,Belgium
,
Iordanis Milionis
Affiliations:
Janssen, Pharmaceutical Companies of Johnson & Johnson,Beerse,Belgium
Uwe Platzbecker
Affiliations:
Medizinische Klinik und Poliklinik I,Dresden,Germany
EHA Learning Center. Fenaux P. Jun 10, 2016; 133235
Prof. Pierre Fenaux
Prof. Pierre Fenaux

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Abstract: P248

Type: Poster Presentation

Presentation during EHA21: On Friday, June 10, 2016 from 17:15 - 18:45

Location: Poster area (Hall H)

Background
Erythropoiesis stimulating agents (ESA) are first choice for treating anemia in lower-risk MDS patients (pts), but no ESA is approved for this indication. This international, Phase 3, randomized, double-blind, placebo (PBO)-controlled, multicenter study assessed the efficacy and safety of epoetin-alfa (epoetin-a; Eprex®) in pts with IPSS Low- or Int-1 risk MDS suffering from anemia.

Aims
To evaluate whether epoetin-a improves anemia (by erythroid response [ER]; IWG 2006) vs PBO over 24 weeks (w) of treatment. Duration of ER, % of pts maintaining ER up to w48, time to 1st RBC transfusion, transfusion-free interval, # of RBC transfusions, changes in PROs/ QoL and safety were also assessed.

Methods
Pts with de novo IPSS Low or Int-1 MDS with Hb ≤10.0 g/dl, transfusions ≤4 RBC units within 8-w before randomization, baseline serum EPO level <500 mU/mL, adequate iron and vitamin stores were eligible. The study included 3 phases:  3-w screening, 24-w double-blind treatment, and 24-w double-blind treatment extension in responders. Pts were randomized 2:1 to receive either epoetin-a 450 IU/kg (max tot. starting dose 40k IU) or matching PBO, once weekly sc, stratified according to transfusion need (yes/no) & serum EPO level (<200 mU/mL vs ≥200 mU/mL). Dose adjustments driven by ER and weekly Hb levels, included increase up to 1050 IU/kg (max tot. dose 80k IU) and dose reduction/withhold according to weekly Hb regardless of ER status. Primary endpoint was ER during first 24-w based on IWG 2006 criteria by investigators and an independent Response Review Committee (RRC). An ad hoc analysis was conducted in subjects who responded at any time of the study, regardless the IWG 2006 criteria, to allow assessment following dose adjustments and a longer period of observation.

Results
130 pts were randomized, 85 to epoetin-a group; 54.6% were male; median age was 75 years. Baseline characteristics were comparable between groups. 70 (82.4%) epoetin-a pts completed the 24-w treatment; 39 (45.9%) epoetin-a pts entered the extension phase vs 1 (2.2%) PBO pt. 31.8% of epoetin-a pts achieved primary endpoint vs 4.4% of PBO pts, p<0.001. In the ad hoc analysis, 45.9 % of epoetin-a pts vs 4.4 % of PBO pts achieved ER, p<0.001. Median ER duration for epoetin-a pts was 197 days. Within 8-w prior to baseline, 51.8% of epoetin-a pts needed transfusions; this decreased to 24.7% by w-24.  Transfusion need remained unchanged in the PBO pts (48.9% - 54.1%). Time to 1st transfusion was longer in the epoetin-a group (p=0.046). In a post-hoc analysis improvement in QoL scores was observed at w-24 in the epoetin-a arm in responders vs non responders (FACT-An p=0.025, EQ-5D p=0.007, EQ VAS p=0.037). Safety data were comparable up to w24; 77.6% of pts on epoetin-a reported ≥1 treatment-emergent adverse event (TEAE) vs 88.9% with PBO. Drug discontinuation due to AE was 10.6% in epoetin-a vs 13.3% in PBO. 4 pts in the epoetin-a arm (4.7%) and none in PBO reported ≥1 TVE. There were 4 TEAEs with fatal outcome in the epoetin-a arm vs 1 in PBO arm; none was reported to be related to the study drug. During the study progression to AML was similar between groups (3.5% in epoetin-a; 4.4% in PBO).

Conclusion
Epoetin-a significantly improved anemia by increasing Hb and reducing transfusion requirement in patients with Low or Int-1 MDS.  Improved QoL was observed in responders. No new safety signals were detected in this study. These results confirm experience from clinical practice.  

Session topic: Myelodysplastic syndromes - Clinical 1

Keyword(s): Epoetin alfa, MDS
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