Evidence map›Paper›PMID 40377899›Full record

Trial reportAdvances in therapy2025

Long-Term Transfusion Independence with Luspatercept Versus Epoetin Alfa in Erythropoiesis-Stimulating Agent-Naive, Lower-Risk Myelodysplastic Syndromes in the COMMANDS Trial.

Guillermo Garcia-Manero, Valeria Santini, Amer M Zeidan, Rami S Komrokji, Veronika Pozharskaya, Shelonitda Rose, Karen Keeperman, Yinzhi Lai, Sameer Kalsekar, Barkha Aggarwal and 6 more

Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase IIIMulticenter Study
In one paragraph

Trial report in Advances in therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03682536 (A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Luspatercept), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03682536 phase3active not recruitingnot on this map

A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Epoetin Alpha for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Due to Myelodysplastic Syndrome (MDS) in ESA Naïve Subjects Who Require Red Blood Cell Transfusions

TypeinterventionalSponsorCelgeneRan2019 to 2027Enrolled363ConditionsMyelodysplastic SyndromesArmsLuspatercept, Epoetin alfa
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Guillermo Garcia-ManeroMD Anderson Cancer Center, Houston, TX, USA. ggarciam@mdanderson.org.ORCID http://orcid.org/0000-0002-3631-2482
Valeria SantiniMDS Unit, DMSC, University of Florence, AOUC, Florence, Italy.
Amer M ZeidanYale School of Medicine, New Haven, CT, USA.
Rami S KomrokjiMoffitt Cancer Center, Tampa, FL, USA.
Veronika PozharskayaBristol Myers Squibb, Princeton, NJ, USA.
Shelonitda RoseBristol Myers Squibb, Princeton, NJ, USA.
Karen KeepermanBristol Myers Squibb, Princeton, NJ, USA.
Yinzhi LaiBristol Myers Squibb, Princeton, NJ, USA.
Sameer KalsekarBristol Myers Squibb, Hyderabad, India.
Barkha AggarwalBristol Myers Squibb, Princeton, NJ, USA.
Dimana MitevaBristol Myers Squibb, Boudry, Switzerland.
David ValcárcelVall d'Hebron, Institute of Oncology (VHIO), Vall d'Hebron Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
Pierre FenauxAP-HP St Louis, Paris, France.
Jake ShorttMonash Health and Monash University, Clayton, VIC, Australia.
Matteo Giovanni Della PortaHumanitas University, Milan, Italy.
Uwe PlatzbeckerUniversity Hospital Dresden, Dresden, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThe efficacy of erythropoiesis-stimulating agents (ESAs) for transfusion-dependent (TD) anemia in lower-risk myelodysplastic syndromes (LR-MDS) is limited. Luspatercept achieved significantly greater rates of red blood cell (RBC) transfusion independence (TI) versus epoetin alfa (an ESA) in the phase 3 COMMANDS trial. This analysis assessed long-term RBC-TI, cumulative response, and safety with luspatercept in COMMANDS.

methodsEligible patients aged ≥ 18 years, with ESA-naive, RBC TD LR-MDS were randomized 1:1 to receive luspatercept (1.0 mg/kg, titration to 1.75 mg/kg permitted) or epoetin alfa (450 IU/kg, titration to 1050 IU/kg). Disease assessment was carried out at week 24 (day 169) and every 24 weeks thereafter. Treatment continued until disease progression, lack of clinical benefit, unacceptable toxicity, or consent withdrawal.

resultsAt data cutoff (September 22, 2023; median follow-up: luspatercept 21.4 months, epoetin alfa 20.3 months), a greater proportion of patients treated with luspatercept (n = 182) versus epoetin alfa (n = 181) achieved a longest single RBC-TI period ≥ 1 year (44.5% vs. 27.6%; P = 0.0003) and ≥ 1.5 years (30.2% vs. 13.8%; P < 0.0001). Higher rates of RBC-TI ≥ 1.5 years with luspatercept over epoetin alfa were consistent across all prespecified subgroups, including patients with ring sideroblast-negative status and low baseline serum erythropoietin. Longer cumulative RBC-TI response [sum of all durations of RBC-TI for ≥ 12 weeks; week 1 to end of treatment (95% CI)] was observed with luspatercept [154.7 weeks (118.4-NR)] versus epoetin alfa [91.1 weeks (73.1-123.9)]. Rates of treatment-emergent adverse events, including asthenia and hypertension, generally decreased over time in both arms. Progression rates to high-risk MDS and acute myeloid leukemia were similarly low (< 5%) in both treatment arms.

conclusionsThese data demonstrated sustained, durable clinical benefit across subgroups and support luspatercept as the treatment of choice for anemia in patients with LR-MDS who are TD and ESA-naive. TRIAL REGISTRATION NUMBER: NCT03682536.

Indexed as

Activin Receptors, Type IIAnemiaEpoetin AlfaErythrocyte TransfusionHematinicsImmunoglobulin Fc FragmentsMyelodysplastic SyndromesAdultAgedAged, 80 and overBlood TransfusionCD47 AntigenFemaleHumansMaleMiddle AgedActivin Receptors, Type IICD47 AntigenEpoetin AlfaHematinicsImmunoglobulin Fc FragmentsluspaterceptRecombinant Fusion ProteinsAnemiaEpoetin alfaErythroid-stimulating agentsLuspaterceptMyelodysplastic syndromesTransfusion-independence

Identifiers

PMID40377899
PMCPMC12182481

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.