Luspatercept Is FDA Approved As First-Line Treatment for Adults With Transfusion-Dependent, Lower-Risk MDS

Luspatercept Is FDA Approved As First-Line Treatment for Adults With Transfusion-Dependent, Lower-Risk MDS

The FDA has approved luspatercept-aamt (Reblozyl) as a frontline anemia treatment for erythropoiesis-stimulating agent–naïve adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS).¹

This first-line setting approval is supported by findings from the phase 3 COMMANDS trial (NCT03682536), which showed that 58.5% (n = 86) of patients with MDS who received luspatercept achieved red blood cell transfusion independence for at least 12 weeks and experienced a mean hemoglobin increase of at least 1.5 g/dL within the first 24 weeks of treatment. In comparison, only 31.2% (n = 48) of patients receiving epoetin alfa achieved transfusion independence and a meaningful hemoglobin increase (P < .0001). The trial met its primary endpoint, irrespective of patient ring sideroblast status.

“For patients with lower-risk MDS, current standard therapies, including ESAs, have provided limited benefit in controlling anemia with only 1 in 3 patients responding for a duration of 6-18 months,” Guillermo Garcia-Manero, MD, lead investigator and chief of the Section of Myelodysplastic Syndromes at The University of Texas MD Anderson Cancer Center, stated in a press release. “Results from the COMMANDS study showed nearly twice as many patients treated with [luspatercept]achieved transfusion independence of at least 12 weeks and concurrent hemoglobin increase compared to epoetin alfa. Today’s approval represents an important advancement for patients with lower-risk MDS.”

Because MDS are defined by the ineffective production of healthy red blood cells, white blood cells, and platelets, many patents with MDS develop anemia and experience frequently or severe infections. Consequently, many of these patients need blood transfusions—but frequent infusions increase a patient’s risk of iron overload, transfusion reactions, and infections. Red blood cell transfusion-dependency is associated with significantly shorter overall survival in this patient population, in part because of iron overload.

COMMANDS is a phase 3 open-label study which assessed the efficacy and safety of luspatercept compared with epoetin alfa in patients with low-, low- or intermediate-risk myelodysplastic syndrome who were anemic. Patients enrolled in this trial were red blood cell transfusion dependent and had never received erythropoiesis stimulating agents. The primary end point was red blood cell transfusion independence and hemoglobin increase. Key secondary end points were erythroid response for at least 8 weeks during the study, red blood cell transfusion independence for at least 12 weeks, and transfusion independence for 24 weeks.

Ultimately, 74.1% (n = 109) of patients receiving luspatercept achieved erythroid response for at least 8 weeks. In comparison, 51.3% (n = 79) of patients in the epoetin alfa cohort achieved erythroid response (P < .0001). Similarly, 47.6% (n = 70) vs 29.2% (n = 45) of patients, respectively, achieved transfusion independence for at least 24 weeks (P = .0012), and 66.7% (n = 98) vs 46.1% (n = 71) of patients, respectively, achieved transfusion independence for at least 12 weeks (P = .0003).

The recommended treatment dose is 1 mg/kg once every 3 weeks via subcutaneous injection. Prior to each administration, the clinician should review the patient’s hemoglobin results.²

Of note, the agent comes with warnings for thrombosis, hypertension, extramedullary hematopoietic masses, and embryo-fetal toxicity.

The most common adverse events that occurred in the trial were fatigue, headache, musculoskeletal pain, arthralgia, dizziness/vertigo, nausea, diarrhea, cough, abdominal pain, dyspnea, COVID-19, edema peripheral, hypertension, and hypersensitivity.

“The majority of patients with MDS experience chronic anemia and require RBC transfusions,” Tracey Iraca, executive director, MDS Foundation, added. “The approval of [luspatercept]in the first-line treatment of anemia for patients with lower-risk MDS represents a crucial step in making transfusion independence possible for more patients.”¹

References

1. 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 August 28, 2023. https://news.bms.com/news/corporate-financial/2023/U.S.-FDA-Approves-Bristol-Myers-Squibbs-Reblozyl-
2. Reblozyl. Prescribing information. Celgene Corporation, a Bristol-Myers Squibb Company; 2023. Accessed August 29, 2023. https://packageinserts.bms.com/pi/pi_reblozyl.pdf