BENEFIT OF CONTINUING LUSPATERCEPT THERAPY IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES WHO DID NOT ACHIEVE RED BLOOD CELL TRANSFUSION INDEPENDENCE BY WEEK 25 IN THE MEDALIST STUDY
Author(s): ,
Ulrich Germing
Affiliations:
University Hospital of Düsseldorf,Düsseldorf,Germany
,
Pierre Fenaux
Affiliations:
Service d’Hématologie Séniors, Hôpital Saint-Louis, Université Paris 7,Paris,France
,
Uwe Platzbecker
Affiliations:
Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, University Hospital Leipzig,Leipzig,Germany
,
Rena Buckstein
Affiliations:
Odette Cancer Centre, Sunnybrook Health Sciences Centre,Toronto, ON,Canada
,
Valeria Santini
Affiliations:
MDS Unit, Azienda Ospedaliero Universitaria Careggi, University of Florence,Florence,Italy
,
María Díez-Campelo
Affiliations:
Hematology Department,Institute of Biomedical Research of Salamanca, University Hospital of Salamanca,Salamanca,Spain
,
Derek Tang
Affiliations:
Bristol Myers Squibb,Princeton, NJ,United States
,
Rodrigo Ito
Affiliations:
Bristol Myers Squibb,Princeton, NJ,United States
,
Shannon Fabre
Affiliations:
Bristol Myers Squibb,Princeton, NJ,United States
,
Emily Mantovani
Affiliations:
Bristol Myers Squibb,Princeton, NJ,United States
,
George Zhang
Affiliations:
Bristol Myers Squibb,Princeton, NJ,United States
,
Xianwei Ha
Affiliations:
Bristol Myers Squibb,Princeton, NJ,United States
,
Dimana Miteva
Affiliations:
Bristol Myers Squibb,Princeton, NJ,United States
,
Christina Hughes
Affiliations:
Bristol Myers Squibb,Princeton, NJ,United States
,
Wasiulla Khan
Affiliations:
Bristol Myers Squibb,Princeton, NJ,United States
,
Rami S. Komrokji
Affiliations:
Moffitt Cancer Center,Tampa, FL,United States
Guillermo Garcia-Manero
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston, TX,United States
EHA Library. Germing U. 06/09/21; 325673; EP915
Prof. Dr. Ulrich Germing
Prof. Dr. Ulrich Germing
Contributions
Abstract
Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP915

Type: E-Poster Presentation

Session title: Myelodysplastic syndromes - Clinical

Background

MEDALIST (NCT02631070) is an ongoing, randomized, placebo-controlled phase 3 trial evaluating the efficacy and safety of luspatercept, the first and only erythroid maturation agent, in patients with anemia due to lower-risk myelodysplastic syndromes (LR-MDS) with ring sideroblasts. A greater proportion of patients receiving luspatercept than placebo achieved the primary endpoint of red blood cell transfusion independence (RBC-TI) for ≥8 weeks during Weeks 1–24 (Fenaux P, et al. N Engl J Med 2020;382:140-151). However, for patients not achieving the primary endpoint during the first 24 weeks, the value of continuing luspatercept treatment is not yet well understood.

Aims

To evaluate the clinical benefit of continuing luspatercept treatment beyond 24 weeks in patients not achieving the RBC-TI primary endpoint during the first 24 weeks of the MEDALIST study.

Methods

Eligible patients were aged ≥18 years; were refractory, intolerant, or unlikely to respond to erythropoiesis-stimulating agents; and required regular RBC transfusions (≥2 units/8 weeks) in the 16 weeks prior to randomization. Overall, 229 patients were randomized 2:1 to receive either luspatercept (n=153) or placebo (n=76) every 3 weeks through the clinical assessment visit at Week 25, defined as 24 calendar weeks after the first dose, regardless of dose delays. Patients who did not achieve RBC-TI for ≥8 weeks on luspatercept by Week 25 but continued treatment were included in this analysis; the data cutoff was July 1, 2019. For this analysis, transfusion burden, serum ferritin (SF) levels, and hematologic improvement-erythroid (HI-E) response were assessed every 24 weeks. HI-E response was defined as a reduction in RBC transfusions of ≥4 units/8 weeks (for patients with baseline RBC transfusion burden of ≥4 units/8 weeks) or as an increase in hemoglobin level of ≥1.5 g/dL over 8 weeks (for patients with baseline RBC transfusion burden of <4 units/8 weeks).

Results

Of the patients receiving luspatercept, 68 did not meet the primary endpoint during the first 24 weeks and continued treatment. During Weeks 25–48, 16.2% (n=11/68) of these patients achieved RBC‑TI for ≥8 weeks for the first time, and a mean change from baseline of −1.3 RBC units transfused was achieved in 36 pts. 44.1% (n=30/68) of patients who did not meet the primary endpoint achieved any degree of reduction in SF levels from baseline during Weeks 25–48, while 17.9% (n=7/39) shifted from a SF level ≥1,000 µg/L at baseline to <1,000 µg/L. During Weeks 1–48, 60.3% (n=41/68) of patients who did not meet the primary endpoint achieved ≥50% reduction in RBC transfusion burden for ≥8 weeks from baseline and 47.1% (n=32/68) achieved HI-E response. Over the entire treatment period up to the data cutoff, 60.3% (n=41/68) achieved ≥50% reduction in transfusion burden for ≥8 weeks from baseline, 22.1% (n=15/68) achieved RBC-TI for ≥8 weeks, and 48.5% (n=33/68) achieved HI-E response.

Conclusion

A considerable proportion of patients with LR-MDS in the MEDALIST study who did not achieve the primary endpoint, but continued to receive luspatercept beyond 24 weeks of treatment, experienced a broad range of clinical improvements, including reduced transfusion burden, reduced SF levels, and even TI.

Keyword(s): Clinical trial, MDS, Phase III, Transfusion

Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP915

Type: E-Poster Presentation

Session title: Myelodysplastic syndromes - Clinical

Background

MEDALIST (NCT02631070) is an ongoing, randomized, placebo-controlled phase 3 trial evaluating the efficacy and safety of luspatercept, the first and only erythroid maturation agent, in patients with anemia due to lower-risk myelodysplastic syndromes (LR-MDS) with ring sideroblasts. A greater proportion of patients receiving luspatercept than placebo achieved the primary endpoint of red blood cell transfusion independence (RBC-TI) for ≥8 weeks during Weeks 1–24 (Fenaux P, et al. N Engl J Med 2020;382:140-151). However, for patients not achieving the primary endpoint during the first 24 weeks, the value of continuing luspatercept treatment is not yet well understood.

Aims

To evaluate the clinical benefit of continuing luspatercept treatment beyond 24 weeks in patients not achieving the RBC-TI primary endpoint during the first 24 weeks of the MEDALIST study.

Methods

Eligible patients were aged ≥18 years; were refractory, intolerant, or unlikely to respond to erythropoiesis-stimulating agents; and required regular RBC transfusions (≥2 units/8 weeks) in the 16 weeks prior to randomization. Overall, 229 patients were randomized 2:1 to receive either luspatercept (n=153) or placebo (n=76) every 3 weeks through the clinical assessment visit at Week 25, defined as 24 calendar weeks after the first dose, regardless of dose delays. Patients who did not achieve RBC-TI for ≥8 weeks on luspatercept by Week 25 but continued treatment were included in this analysis; the data cutoff was July 1, 2019. For this analysis, transfusion burden, serum ferritin (SF) levels, and hematologic improvement-erythroid (HI-E) response were assessed every 24 weeks. HI-E response was defined as a reduction in RBC transfusions of ≥4 units/8 weeks (for patients with baseline RBC transfusion burden of ≥4 units/8 weeks) or as an increase in hemoglobin level of ≥1.5 g/dL over 8 weeks (for patients with baseline RBC transfusion burden of <4 units/8 weeks).

Results

Of the patients receiving luspatercept, 68 did not meet the primary endpoint during the first 24 weeks and continued treatment. During Weeks 25–48, 16.2% (n=11/68) of these patients achieved RBC‑TI for ≥8 weeks for the first time, and a mean change from baseline of −1.3 RBC units transfused was achieved in 36 pts. 44.1% (n=30/68) of patients who did not meet the primary endpoint achieved any degree of reduction in SF levels from baseline during Weeks 25–48, while 17.9% (n=7/39) shifted from a SF level ≥1,000 µg/L at baseline to <1,000 µg/L. During Weeks 1–48, 60.3% (n=41/68) of patients who did not meet the primary endpoint achieved ≥50% reduction in RBC transfusion burden for ≥8 weeks from baseline and 47.1% (n=32/68) achieved HI-E response. Over the entire treatment period up to the data cutoff, 60.3% (n=41/68) achieved ≥50% reduction in transfusion burden for ≥8 weeks from baseline, 22.1% (n=15/68) achieved RBC-TI for ≥8 weeks, and 48.5% (n=33/68) achieved HI-E response.

Conclusion

A considerable proportion of patients with LR-MDS in the MEDALIST study who did not achieve the primary endpoint, but continued to receive luspatercept beyond 24 weeks of treatment, experienced a broad range of clinical improvements, including reduced transfusion burden, reduced SF levels, and even TI.

Keyword(s): Clinical trial, MDS, Phase III, Transfusion

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