Luspatercept-aamt Shows Efficacy Treating Anemia Due to Myelodysplastic Syndromes

Bristol Myers Squibb has announced the first results from the phase 3 COMMANDS study (NCT03682536) evaluating luspatercept-aamt (Reblozyl) compared to epoetin alfa for the treatment of anemia in individuals with very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS), who require red blood cell (RBC) transfusions, and are erythropoiesis stimulating agent (ESA)-naïve. These results were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting and as an oral presentation during the European Hematology Association (EHA) Congress.

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“Results from the COMMANDS study showed treatment with [luspatercept-aamt] compared to epoetin alfa led to superior and statistically significant improvements in [RBC] transfusion independence and hemoglobin increase, improvements in response durability, and equal or better outcomes across all subgroups, with acceptable safety and tolerability for patients with ESA-naïve, lower-risk MDS,” Guillermo Garcia-Manero, MD, chief of the Section of Myelodysplastic Syndromes at The University of Texas MD Anderson Cancer Center, said in a statement.

Study investigators randomized individuals aged 18 years and older with lower-risk MDS requiring transfusions to receive subcutaneous luspatercept-aamt once every 3 weeks of epoetin alfa weekly for 24 weeks or more. A total of 147 individuals received luspatercept-aamt and 154 received epoetin alfa, with a median treatment duration of 41.6 weeks and 27 weeks, respectively.

The results demonstrated that 58.5% of individuals receiving luspatercept-aamt achieved the primary endpoint of RBC transfusion independence (RBC-TI) of at least 12 weeks with a concurrent mean hemoglobin increase of at least 1.5 g/dL within the first 24 weeks compared to 31.2% of individuals receiving epoetin alfa.

Additionally, approximately 74.1% of individuals treated with luspatercept-aamt achieved the secondary endpoint of an erythroid response increase of at least 8 weeks compared to 51.3% of those on epoetin alfa.

Investigators also found that those treated with luspatercept-aamt achieved more durable responses, with a median duration of response of RBC-TI 12 weeks or greater of 126.6 weeks compared to 77 weeks with epoetin alfa. In first 24 weeks of treatment, RBC-TI of at least 24 weeks was achieved by 47.6% of those receiving luspatercept-aamt and 29.2% receiving epoetin alfa. The benefits of luspatercept-aamt were relevant across subgroups and no new safety signals were identified.

“Clinical experience has demonstrated that just 1 in 3 patients with low-risk [MDS] experience responses to erythroid stimulating agents over 6 [to] 18 months, leaving a significant need for more effective options to address chronic anemia,” Matteo Giovanni Della Porta, head of Leukemia Unit at Humanitas Cancer Center in Milan, Italy, said in the statement. “In the COMMANDS study, the median duration of red blood cell transfusion independence was nearly 1 year longer with [luspatercept-aamt] than with epoetin alfa and showed safety consistent with its known profile, demonstrating its potential as a first-line treatment in patients with transfusion-dependent, very low- to intermediate-risk MDS.”

Efficacy and safety results demonstrated favorable outcomes for luspatercept-aamt compared to epoetin alfa across common MDS mutations. The findings also showed a higher probability of achieving clinical benefit, regardless of overall mutational burden, according to the statement.

A supplemental biologics license application is currently under priority review by the FDA for the treatment of anemia in ESA-naïve adults with very low- to intermediate-risk MDS who may require RBC transfusions. There is a Prescription Drug User Fee Act goal date of August 28, 2023.

Additionally, the European Medicines Agency has validated the Type II Variation for this patient population. Luspatercept-aamt is currently being developed and commercialized through a collaboration with Merck.

Reference

Bristol Myers Squibb to present first results at ASCO and EHA from phase 3 COMMANDS study of Reblozyl (luspatercept-aamt) in first-line treatment of anemia in adults with lower-risk myelodysplastic syndromes (MDS). News release. Business Wire. May 25, 2023. Accessed June 19, 2023. https://www.businesswire.com/news/home/20230524005878/en/Bristol-Myers-Squibb-to-Present-First-Results-at-ASCO-and-EHA-from-Phase-3-COMMANDS-Study-of-Reblozyl%C2%AE-luspatercept-aamt-in-First-Line-Treatment-of-Anemia-in-Adults-with-Lower-Risk-Myelodysplastic-Syndromes-MDS