Lower-risk myelodysplastic syndromes (LR-MDS) are a group of chronic bone marrow disorders characterized by ineffective blood cell production, most commonly leading to debilitating, symptomatic anemia.¹ For many patients, managing this anemia necessitates frequent red blood cell (RBC) transfusions, which can require time-consuming hospital visits and carry risks of iron overload and other complications. Management can also include treatment with erythropoiesis-stimulating agents (ESAs), however response rates to first-line treatment with ESAs in LR-MDS range from 30% to 60%.² While these patients are categorized as 'lower-risk,' they can still experience reduced overall survival (OS) compared to the general population.

At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, researchers presented OS and long-term TI data (>3 years) for Reblozyl^® (luspatercept-aamt) in patients with ESA-naive transfusion-dependent LR-MDS. These findings, from the Phase 3 COMMANDS trial, provide further information on the role of Reblozyl as a foundational first-line treatment option for anemia in LR-MDS. The COMMANDS trial compared Reblozyl versus epoetin alfa for the treatment of anemia in RBC-dependent, lower-risk myelodysplastic syndromes (MDS) patients. Reblozyl is a prescription medicine indicated for the treatment of anemia (low red blood cells) in adults with MDS who may need regular RBC transfusions and have never received an ESA. Reblozyl is not for use as a substitute for RBC transfusions in people who need immediate treatment for anemia. It is not known if Reblozyl is safe or effective in children. Please see below for Important Safety Information.

About the Phase 3 COMMANDS trial^3-5:

COMMANDS (N=356) was a head-to-head trial that compared Reblozyl versus EA in adult patients with anemia due to IPSS-R very low-, low-, or intermediate-risk MDS, with or without RS, who were ESA-naive (without endogenous sEPO levels <500 U/L) and required RBCT. Patients with del(5q) and those previously treated with disease-modifying agents of HMAs were excluded. Patients were randomized to either Reblozyl (n=178) 1mg/kg SC Q3W, with titration to max 1.75 mg/kg if needed to achieve response, or EA (n=178) 450 IU/kg SC Q1W with titration up to 1,050 IU/kg if needed (maximum total dose of 80,000 IU). Both treatments were dose modified targeting Hgb 10-12 g/dL and TI.^3-5

• Primary endpoint³: 58.5% of patients taking Reblozyl (n=86/147; 95% CI: 50.1, 66.6) achieved the primary composite endpoint of ≥12 week RBC-TI and Hgb increase ≥1.5 g/dL vs 31.2% of patients taking EA (n=48/154; 95% CI: 24.0, 39.1)
• Key secondary endpoints³:
  • HI-E per IWG ≥8wks (Wks 1-24): 74.1% of patients taking Reblozyl (n=109/147) vs. 51.3% of patients taking EA (n=79/154)
  • RBC-TI for 24 wks (Wks 1-24): 47.6% of patients taking Reblozyl (70/147) vs 29.2% of patients taking EA (n=45/154)
  • RBC-TI for ≥12wks (Wks 1-24): 66.7% of patients taking Reblozyl (n=98/147) vs 46.1% of patients taking EA (n=71/154)

Reblozyl is associated with the following Warnings and Precautions: Thrombosis/Thromboembolism, Hypertension, and Embryo-Fetal Toxicity. In ESA-naïve adult patients with Myelodysplastic Syndromes, Grade >3 (>2%) adverse reactions included hypertension and dyspnea. The most common (>10%) all-grade adverse reactions included diarrhea, fatigue, hypertension, peripheral edema, nausea, and dyspnea. Please see additional Important Safety Information below.

A look at the results from COMMANDS at >3 years of follow-up⁶:

At a median (range) duration of follow-up of 35.9 (1-73) months for those treated with Reblozyl and 30.8 (0-77) months for those treated with EA, the analysis found that median OS, a secondary endpoint, in the intent-to-treat (ITT) population has not been reached for those treated with Reblozyl vs 46.0 months for those treated with EA [Hazard Ratio (95% CI) 0.781 (0.559-1.092)]; this OS analysis was calculated from an unstratified Kaplan-Meier method. HR was calculated by a stratified Cox proportional hazard model. Stratification factors were baseline RBC TB (<4, ≥4 pRBC U/8 weeks), RS status (+, −), and sEPO levels (≤200, >200 U/L). Derived stratification factors were used. Treatment-emergent included adverse events that started on or after the first dose until 42 days after the last dose, as well as those SAEs made known to the investigator at any time thereafter that were suspected of being related to injection.

• Analysis was not powered to show a statistically significant difference; analysis was conducted without controlling for type I error rate
• These analyses should not be interpreted to determine treatment differences between arms in these subgroups because of limited sample size, lack of statistical hypothesis testing, and the increased probability of a false-positive finding
• Extended follow-up is needed to confirm results and explore baseline characteristics associated with improved survival

An investigator's perspective

These insights are crucial for both the scientific community and, more importantly, for the patients whose lives are directly impacted. For clinicians, these long-term data points help provide clarity on Reblozyl’s role within the treatment paradigm for anemia in LR-MDS and further evidence for its clinical utility.

Commenting on these longer-term follow-up results, Dr. Guillermo Garcia-Manero, M.D., lead investigator, Chair of Leukemia, Chief of the Section of Myelodysplastic Syndromes at The University of Texas MD Anderson Cancer Center and lead author, stated: “In anemia associated with lower-risk myelodysplastic syndromes, treatment goals balance symptom management and achieving durable transfusion independence. This long-term overall survival data provides further information on the role of Reblozyl as a first-line therapy.”

Bristol Myers Squibb remains committed to continuing to understand the full potential of Reblozyl and to advancing therapies that can impact the lives of those facing serious diseases.