EHA Library - The official digital education library of European Hematology Association (EHA)

EFFECTS OF LUSPATERCEPT ON SERUM FERRITIN IN PATIENTS (PTS) WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES (MDS) WITH RING SIDEROBLASTS (RS) IN THE PHASE 3 MEDALIST TRIAL
Author(s): ,
Pierre Fenaux
Affiliations:
Service d'Hématologie Séniors,Hôpital Saint-Louis, Université Paris 7,Paris,France
,
Valeria Santini
Affiliations:
MDS Unit,Azienda Ospedaliero Universitaria (AOU) Careggi, University of Florence,Florence,Italy
,
Ghulam J. Mufti
Affiliations:
Department of Haemato-Oncology,King's College London,London,United Kingdom
,
María Diez-Campelo
Affiliations:
Hematology Department,Institute of Biomedical Research of Salamanca, University Hospital of Salamanca,Salamanca,Spain
,
Carlo Finelli
Affiliations:
Department of Oncology and Hematology,S. Orsola-Malpighi University Hospital,Bologna,Italy
,
Mikkael A. Sekeres
Affiliations:
Department of Hematology and Medical Oncology,Cleveland Clinic,Cleveland, OH,United States
,
Bruno Quesnel
Affiliations:
Service des Maladies du Sang,Hôpital Huriez, Centre Hospitalier Universitaire de Lille,Lille,France
,
Odile Beyne-Rauzy
Affiliations:
Médicine Interne,Institute Universitaire du Cancer de Toulouse Oncopole,Toulouse,France
,
Guillermo Garcia-Manero
Affiliations:
Department of Leukemia,University of Texas MD Anderson Cancer Center,Houston, TX,United States
,
Rami S. Komrokji
Affiliations:
Moffitt Cancer Center,Tampa,United States
,
Rena Buckstein
Affiliations:
Odette Cancer Centre,Sunnybrook Health Sciences Centre,Toronto, ON,Canada
,
Maria Teresa Voso
Affiliations:
Dipartimento di Biopatologia e Diagnostica per Immagini,University of Rome Tor Vergata,Rome,Italy
,
Dominik Selleslag
Affiliations:
Department of Haematology,AZ Sint-Jan,Bruges,Belgium
,
Amy E. DeZern
Affiliations:
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins,Baltimore, MD,United States
,
Peter L. Greenberg
Affiliations:
Stanford University Cancer Center,Stanford, CA,United States
,
Amer M. Zeidan
Affiliations:
Department of Internal Medicine,Yale School of Medicine and Yale Cancer Center, Yale University,New Haven, CT,United States
,
Lionel Adès
Affiliations:
Service d'Hématologie Séniors,Hôpital Saint-Louis, Université Paris 7,Paris,France
,
Amit Verma
Affiliations:
Department of Oncology,Albert Einstein College of Medicine, Montefiore Medical Center,Bronx, NY,United States
,
Michael R. Savona
Affiliations:
Vanderbilt-Ingram Cancer Center,Vanderbilt University School of Medicine,Nashville, TN,United States
,
Abderrahmane Laadem
Affiliations:
Bristol-Myers Squibb,Summit, NJ,United States
,
Rodrigo Ito
Affiliations:
Bristol-Myers Squibb,Summit, NJ,United States
,
Jennie Zhang
Affiliations:
Bristol-Myers Squibb,Summit, NJ,United States
,
Anita Rampersad
Affiliations:
Bristol-Myers Squibb,Summit, NJ,United States
,
Daniel Sinsimer
Affiliations:
Bristol-Myers Squibb,Summit, NJ,United States
,
Jessica Morison
Affiliations:
Bristol-Myers Squibb,Summit, NJ,United States
,
Chrystal Louis
Affiliations:
Bristol-Myers Squibb,Summit, NJ,United States
,
Peter G. Linde
Affiliations:
Acceleron Pharma,Cambridge, MA,United States
Uwe Platzbecker
Affiliations:
Medical Clinic and Policlinic 1, Hematology and Cellular Therapy,University Hospital Leipzig,Leipzig,Germany
(Abstract release date: 05/14/20) EHA Library. Fenaux P. 06/12/20; 294724; EP807
Prof. Pierre Fenaux
Prof. Pierre Fenaux
Contributions
Abstract

Abstract: EP807

Type: e-Poster

Background
Iron overload resulting from red blood cell (RBC) transfusions is associated with significant morbidity in pts with MDS. In MDS with RS, iron overload may also occur prior to RBC transfusions, due to ineffective erythropoiesis. The safety and efficacy of luspatercept, a first-in-class erythroid maturation agent, is being assessed in the randomized, placebo (PBO)-controlled, phase 3 MEDALIST trial of pts with lower-risk MDS with RS (NCT02631070).

Aims
To assess changes from baseline (BL) in serum ferritin and iron chelation therapy (ICT) use in pts in the MEDALIST trial.

Methods
Pts had IPSS-R-defined Very low-, Low-, or Intermediate-risk MDS; were ≥18 y old; had unsatisfactory response to or were ineligible for EPO-based therapy; and required regular RBC transfusions. All pts provided informed written consent. Luspatercept (1.0 mg/kg, titration up to 1.75 mg/kg if needed) or PBO was administered subcutaneously every 3 wks.

Results
Of 153 luspatercept-treated pts, 87 (56.9%) and 66 (43.1%) pts had BL RBC transfusion burden <6 U/8 wks and ≥6 U/8 wks, respectively, vs 43 (56.6%) and 33 (43.4%) of 76 PBO pts. Median BL serum ferritin (range) was 1089.2 (64–5968) vs 1122.1 (165–5849) μg/L in luspatercept vs PBO arms. In pts with BL transfusion burden ≥6 U/8 wks, median (range) BL serum ferritin was 1306.1 (64–5968) vs 1492.9 (256–5280) μg/L in luspatercept vs PBO arms. 71 (46.4%) and 40 (52.6%) pts in luspatercept and PBO arms, respectively, received ICT at BL, including 50/66 (75.8%) luspatercept pts and 26/33 (78.8%) PBO pts with BL transfusion burden ≥6 U/8 wks.

A decrease from BL in mean serum ferritin was observed with luspatercept vs PBO in Wks 9–24 (least squares [LS] mean −2.7 vs +226.5 μg/L; P=0.0024) and Wks 33–48 (LS mean −72.0 vs +247.4 μg/L; P=0.0294). A difference in mean serum ferritin change from BL was also observed in luspatercept-treated pts not achieving hematologic improvement–erythroid (HI-E) in Wks 1–24 vs PBO (LS mean +73.4 vs +244.2 μg/L; P=0.0777). In luspatercept-treated pts with BL transfusion burden ≥6 U/8 wks, a decrease from BL in mean serum ferritin in Wks 9–24 was observed vs PBO (LS mean −63.5 vs 271.2 μg/L; P=0.0103). In luspatercept-treated pts with BL transfusion burden ≥6 U/8 wks who achieved HI-E in Wks 1–24, LS mean change from BL in serum ferritin in Wks 9–24 was −111.4 μg/L and in Wks 33–48 was −124.4 μg/L. In pts with BL transfusion burden ≥6 U/8 wks, a difference in mean serum ferritin change from BL in Wks 9–24 was also observed in luspatercept-treated pts not achieving HI-E in Wks 1–24 vs PBO (LS mean +3 vs +344.3 μg/L; P=0.0452).

LS mean change from BL in mean daily ICT dose in pts receiving luspatercept was 10.0 mg/d over Wks 9–24 and −148.8 mg/d over Wks 33–48. In luspatercept-treated pts with BL transfusion burden ≥6 U/8 wks, mean change from BL in mean daily ICT dose was −68.5 mg/d over Wks 9–24 and −327.1 mg/d over Wks 33–48.

Conclusion
Luspatercept treatment resulted in serum ferritin decreases, particularly in pts with higher BL transfusion burden and in those with high BL serum ferritin who experienced significant RBC transfusion reduction. This suggests that the effect of luspatercept on serum ferritin may be due not only to transfusion reduction, but also potentially to a more direct effect of the drug on ineffective erythropoiesis and/or iron metabolism. Overall, ICT use was reduced with luspatercept.

Session topic: 10. Myelodysplastic syndromes - Clinical

Keyword(s): Clinical trial, Ferritin, Iron, MDS

Abstract: EP807

Type: e-Poster

Background
Iron overload resulting from red blood cell (RBC) transfusions is associated with significant morbidity in pts with MDS. In MDS with RS, iron overload may also occur prior to RBC transfusions, due to ineffective erythropoiesis. The safety and efficacy of luspatercept, a first-in-class erythroid maturation agent, is being assessed in the randomized, placebo (PBO)-controlled, phase 3 MEDALIST trial of pts with lower-risk MDS with RS (NCT02631070).

Aims
To assess changes from baseline (BL) in serum ferritin and iron chelation therapy (ICT) use in pts in the MEDALIST trial.

Methods
Pts had IPSS-R-defined Very low-, Low-, or Intermediate-risk MDS; were ≥18 y old; had unsatisfactory response to or were ineligible for EPO-based therapy; and required regular RBC transfusions. All pts provided informed written consent. Luspatercept (1.0 mg/kg, titration up to 1.75 mg/kg if needed) or PBO was administered subcutaneously every 3 wks.

Results
Of 153 luspatercept-treated pts, 87 (56.9%) and 66 (43.1%) pts had BL RBC transfusion burden <6 U/8 wks and ≥6 U/8 wks, respectively, vs 43 (56.6%) and 33 (43.4%) of 76 PBO pts. Median BL serum ferritin (range) was 1089.2 (64–5968) vs 1122.1 (165–5849) μg/L in luspatercept vs PBO arms. In pts with BL transfusion burden ≥6 U/8 wks, median (range) BL serum ferritin was 1306.1 (64–5968) vs 1492.9 (256–5280) μg/L in luspatercept vs PBO arms. 71 (46.4%) and 40 (52.6%) pts in luspatercept and PBO arms, respectively, received ICT at BL, including 50/66 (75.8%) luspatercept pts and 26/33 (78.8%) PBO pts with BL transfusion burden ≥6 U/8 wks.

A decrease from BL in mean serum ferritin was observed with luspatercept vs PBO in Wks 9–24 (least squares [LS] mean −2.7 vs +226.5 μg/L; P=0.0024) and Wks 33–48 (LS mean −72.0 vs +247.4 μg/L; P=0.0294). A difference in mean serum ferritin change from BL was also observed in luspatercept-treated pts not achieving hematologic improvement–erythroid (HI-E) in Wks 1–24 vs PBO (LS mean +73.4 vs +244.2 μg/L; P=0.0777). In luspatercept-treated pts with BL transfusion burden ≥6 U/8 wks, a decrease from BL in mean serum ferritin in Wks 9–24 was observed vs PBO (LS mean −63.5 vs 271.2 μg/L; P=0.0103). In luspatercept-treated pts with BL transfusion burden ≥6 U/8 wks who achieved HI-E in Wks 1–24, LS mean change from BL in serum ferritin in Wks 9–24 was −111.4 μg/L and in Wks 33–48 was −124.4 μg/L. In pts with BL transfusion burden ≥6 U/8 wks, a difference in mean serum ferritin change from BL in Wks 9–24 was also observed in luspatercept-treated pts not achieving HI-E in Wks 1–24 vs PBO (LS mean +3 vs +344.3 μg/L; P=0.0452).

LS mean change from BL in mean daily ICT dose in pts receiving luspatercept was 10.0 mg/d over Wks 9–24 and −148.8 mg/d over Wks 33–48. In luspatercept-treated pts with BL transfusion burden ≥6 U/8 wks, mean change from BL in mean daily ICT dose was −68.5 mg/d over Wks 9–24 and −327.1 mg/d over Wks 33–48.

Conclusion
Luspatercept treatment resulted in serum ferritin decreases, particularly in pts with higher BL transfusion burden and in those with high BL serum ferritin who experienced significant RBC transfusion reduction. This suggests that the effect of luspatercept on serum ferritin may be due not only to transfusion reduction, but also potentially to a more direct effect of the drug on ineffective erythropoiesis and/or iron metabolism. Overall, ICT use was reduced with luspatercept.

Session topic: 10. Myelodysplastic syndromes - Clinical

Keyword(s): Clinical trial, Ferritin, Iron, MDS

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies