Luspatercept Latest Research for Lower-Risk MDS

Luspatercept (Reblozyl, Bristol Myers Squibb) is a medication used to treat anemia and reduce the need for blood transfusions. It was approved as a first-line treatment for people with low- and intermediate-risk myelodysplastic syndromes (MDS) in 2023 based on results from the COMMANDS trial. At the 2025 American Society of Clinical Oncology (ASCO) and European Hematology Association (EHA) conferences, researchers presented new data showing luspatercept’s efficacy in different settings. 

This article highlights five studies that offer insight into how this therapy affects red blood cell production, transfusion independence, and quality of life for people with lower-risk MDS.

Luspatercept shows strong benefits in patients with low transfusion burden

A meta-analysis of four clinical trials that included 700 people with lower-risk, transfusion-dependent MDS evaluated how luspatercept helped those who did not respond to erythropoiesis-stimulating agents (ESA). Luspatercept improved red blood cell counts (known as hematological improvement erythroid) in 61% of patients for 8 weeks or more. About 49% did not need blood transfusions for 8 weeks or more. 

Notably, patients with a low transfusion burden had better results. Of the patients who needed less than four units of blood in 8 weeks,  78% became transfusion-free after treatment with luspatercept compared to just 21% with a high transfusion burden. Additionally, 53% experienced a hemoglobin increase of at least 1 g/dL. Nearly half of the people treated with luspatercept remained transfusion-free for 12 weeks or more.

These results show that luspatercept can significantly reduce the need for transfusions and improve anemia-related symptoms, especially in patients with fewer transfusion needs to start.

Larger review confirms luspatercept’s role in reducing transfusion needs

Another systematic review included 13 studies and 2,614 patients, most of whom had transfusion-dependent MDS and received luspatercept. About 52% of patients achieved transfusion independence at 8 weeks, and 45.6% did so at 12 weeks. The therapy was more effective in those with ring sideroblasts and in patients who did not respond to previous anemia treatments.

Reported side effects included swelling in the hands, legs, or feet (18.8%), fatigue (16.8%), and back pain (16.1%). A small number (2.6%) progressed to acute myeloid leukemia. This study helps confirm luspatercept’s role in managing anemia for patients who have not improved with other options, though side effects should be monitored.

COMMANDS Trial: Luspatercept more effective than epoetin alfa

The COMMANDS trial compared luspatercept to epoetin alfa in people with lower-risk MDS who had not yet received any ESAs. Epoetin alfa is a common anemia treatment. 

There were 363 people enrolled in the COMMANDS trial. Of those, 182 were treated with luspatercept and 181 were treated with epoetin alfa. Among those receiving luspatercept, 76.4% became transfusion-independent for at least 12 weeks, compared to 55.8% in the epoetin alfa group. The time patients remained transfusion-free was also longer: 187 weeks with luspatercept versus 95 weeks with epoetin alfa.

Five-year overall survival was higher for patients on luspatercept (54%) than those on epoetin alfa (41.8%). These findings suggest luspatercept may be more effective as a first treatment option for anemia in lower-risk MDS.

Real-world study reflects strong clinical benefits

A real-world study looked at outcomes in 103 patients who began first-line treatment with either luspatercept or an ESA after luspatercept became available. Of the 46 patients who received luspatercept, 89.1% had a hemoglobin increase of at least 1.5 g/dL, compared to 56.1% in the ESA group. Among transfusion-dependent patients, 91.7% on luspatercept became transfusion-free within 3 months, compared to 71.4% in the ESA group.

This real-world data supports results from earlier clinical trials, reinforcing luspatercept’s value in reducing transfusion needs and improving anemia in everyday clinical settings.

Targeted benefit in patients with del(5q) MDS

An interim report from the QOL-ONE PHOENIX trial examined 22 adults with a specific type of MDS marked by deletion 5q, all of whom were transfusion-dependent and had not benefited from prior therapies such as lenalidomide. 

After 24 weeks of luspatercept treatment, 6 of 13 evaluable patients (46%) became transfusion-free for at least 8 weeks. One additional patient had a notable reduction in transfusion needs. Most patients reported an improvement in hemoglobin levels and quality of life.

These early results highlight that luspatercept may provide a valuable option for people with del(5q) MDS, a group with fewer treatment choices and more difficult disease features.

Roundup summary 

Across multiple studies, luspatercept consistently improved hemoglobin levels and reduced the need for regular blood transfusions in patients with lower-risk MDS. It may be especially helpful for those who have not responded to other treatments or who have specific features like ring sideroblasts or del(5q) changes. Understanding how different patient groups respond to luspatercept can help guide personalized treatment decisions.

Keep reading more news on conferences, treatment advances and more, stay tuned in the HealthTree News site. 

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Sources: 

• Unveiling the promising potential of luspatercept in transfusion-dependent lower-risk myelodysplastic syndromes: A systematic review and meta-analysis. 
• Luspatercept in patients with lower-risk myelodysplastic syndromes (MDS): A systematic review and meta-analysis.
• Real-world (RW) outcomes of patients (pts) with lower-risk myelodysplastic syndrome (LR-MDS) receiving first-line (1L) luspatercept (LUSPA) or 1L erythropoiesis-stimulating agents (ESA) in the US. 
• Overall survival (OS) and duration of response for transfusion independence (TI) in erythropoiesis stimulating agent (ESA)–naive patients (pts) with very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS) treated with luspatercept (LUSPA) vs epoetin alfa (EA) in the COMMANDS trial.
• LUSPATERCEPT FOR THE TREATMENT OF TRANSFUSION-DEPENDENT ANEMIA IN PATIENTS WITH MYELODYSPLASTIC NEOPLASMS WITH DEL5Q, REFRACTORY/RESISTANT/INTOLERANT TO PRIOR TREATMENTS (QOL-ONE PHOENIX)