European Commission Approves Frontline Luspatercept for Transfusion-Dependent Anemia in Lower-Risk MDS

The European Commission has expanded its approval of luspatercept-aamt (Reblozyl) to include frontline treatment of adult patients with transfusion-dependent anemia due to very low–, low-, and intermediate-risk myelodysplastic syndrome (MDS).¹ This marks the fourth authorized indication for luspatercept in Europe and covers all European Union (EU) member states.

This regulatory decision was supported by findings from the phase 3 COMMANDS trial (NCT03682536), in which treatment with luspatercept met the primary end point of 12-week red blood cell (RBC) transfusion independence with a mean hemoglobin increase of at least 1.5 g/dL in patients with anemia due to MDS of low- to intermediate-risk who were RBC transfusion dependent and naive to erythropoietin stimulating agents (ESAs). At the time of the primary analysis, with a data cutoff of March 31, 2023, 60.4% (n = 110) of patients in the luspatercept arm vs 34.8% (n = 63) of those in the epoetin alfa arm achieved RBC transfusion independence for at least 12 weeks with a concurrent mean hemoglobin increase of at least 1.5 g/dL within the first 24 weeks (P < .0001).

“In the treatment of lower-risk MDS, few patients experience a lasting response to ESAs, leaving a critical need for more effective treatment options to address the burden of their anemia,” Matteo Giovanni Della Porta, MD, study investigator and head of the Leukemia Unit at Humanitas Cancer Center in Milan, Italy, stated in a news release. “Results from the COMMANDS study underscore the clinical value of [luspatercept] as an initial treatment for anemia in patients with low- to intermediate-risk MDS, and this approval represents a significant milestone towards improving treatment practice and offering better outcomes for patients.”

In COMMANDS, 363 patients at least 18 years of age were randomly assigned in a 1:1 fashion to receive subcutaneous luspatercept at a starting dose of 1.0 mg/kg with titration up to 1.75 mg/kg once every 3 weeks or epoetin alfa at a starting dose of 450 IU/kg with titration up to 1050 IU/kg weekly for at least 24 weeks.

Key secondary end points in COMMANDS included erythroid response of at least 8 weeks during weeks 1 through 24 of the trial, RBC transfusion independence for at least 12 weeks, and RBC transfusion independence for 24 weeks.

An erythroid increase lasting at least 8 weeks was observed in 74.2% (n = 135) of patients who received luspatercept vs 53% (n = 96) of those who received epoetin alfa (P < .0001). RBC transfusion independence of at least 12 weeks was reported in 68.1% (n = 124) and 48.6% (n = 88) of patients in the luspatercept and epoetin alfa arms, respectively (P < .0001). The duration of response was 128.1 weeks (95% CI, 108.3-NE) with luspatercept vs 89.7 weeks (95% CI, 55.9-157.3) with epoetin alfa in patients who achieved transfusion independence for at least 12 weeks during weeks 1 through 24 (HR, 0.534; 95% CI, 0.330-0.864; P = .0096).

Safety findings from COMMANDS were consistent with those observed in prior MDS studies and aligned with expected symptoms of patients in the trial population. Rates of patients who progressed to acute myeloid leukemia and the total number of deaths were similar between both study arms. The most common treatment-emergent adverse effects that occurred in at least 10% of patients included fatigue, diarrhea, hypertension, COVID-19, dyspnea, peripheral edema, nausea, asthenia, anemia, dizziness, headache, and back pain. Reported asthenia and fatigue rates decreased over time.

“With this approval for [luspatercept] as a first-line treatment for anemia in adults with lower-risk MDS, more patients in the EU will have the potential to become transfusion independent for longer periods of time compared to current options available,” Monica Shaw, MD, senior vice president and head of European Markets at Bristol Myers Squibb, added in the news release. “This milestone underscores our ongoing commitment to developing new options for patients with disease-related anemia.”

In 2023, luspatercept received FDA approval for the first-line treatment of anemia in patients with lower-risk MDS who were naive to ESAs and may require regular RBC transfusions.² The agent was also approved in Japan for this indication.¹

References

1. European Commission expands approval of Bristol Myers Squibb’s Reblozyl (luspatercept) to include first-line treatment of transfusion-dependent anemia in adults with lower-risk myelodysplastic syndromes (LR-MDS). News release. Bristol Myers Squibb. April 2, 2024. Accessed April 3, 2024. https://news.bms.com/news/corporate-financial/2024/European-Commission-Expands-Approval-of-Bristol-Myers-Squibbs-Reblozyl-luspatercept-to-Include-First-Line-Treatment-of-Transfusion-Dependent-Anemia-in-Adults-with-Lower-Risk-Myelodysplastic-Syndromes-LR-MDS/default.aspx
2. US FDA approves Bristol Myers Squibb's Reblozyl (luspatercept-aamt) as first-line treatment of anemia in adults with lower-risk myelodysplastic syndromes who may require transfusions. News release. Bristol Myers Squibb. August 28, 2023. Accessed April 3, 2024. https://news.bms.com/news/details/2023/U.S.-FDA-Approves-Bristol-Myers-Squibbs-Reblozyl-luspatercept-aamt-as-First-Line-Treatment-of-Anemia-in-Adults-with-Lower-Risk-Myelodysplastic-Syndromes-MDS-Who-May-Require-Transfusions/default.aspx