Presentation of the COMMANDS trial offered practice-changing results for luspatercept.
COMMANDS: Luspatercept Boosts Population With Lower-Risk Myelodysplastic Syndromes Who Are Freed From Blood Transfusions
More patients at risk of anemia from lower-risk myelodysplastic syndromes (MDS) were able to avoid blood transfusions for at least 12 weeks when taking luspatercept (Reblozyl) compared with epoetin alfa, according to data from the COMMANDS trial (NCT03682536), which was presented on the first day of the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.1
“Transfusions are a significant burden to our patients based on the time spent in transfusion units, the potential for infectious complications, iron accumulation, transfusion reactions that can be quite severe, and eventually failure to respond to the transfusions. In addition, transfusions have a significant economic impact,” principal investigator Guillermo Garcia-Manero, MD, of The University of Texas MD Anderson Cancer Center, who presented the COMMANDS trial data in an oral session June 2, said in a statement from ASCO.2
“The COMMANDS results could transform how we approach the treatment of anemia in patients with lower-risk MDS,” said Garcia-Manero, who is professor in the Department of Leukemia and chief of the Section of Myelodysplastic Syndromes at MD Anderson in Houston.
He noted that erythropoietin stimulating agents (ESAs) have been the first-line therapy for decades, but these results “could represent the standard of care as first-line therapy for a significant fraction of patients with anemia and lower-risk disease.”
COMMANDS is a global phase 3 trial that enrolled 354 adult patients with lower-risk MDS who required red blood cell transfusions but who had not yet received ESAs. The study participants were assigned to 2 groups:
One group (178 patients) received luspatercept by injection every 3 weeks for at least 24 weeks.
One group (176 patients) received epoetin alfa (an ESA) by injection once weekly for at least 24 weeks.1
After a median of 41.6 weeks for luspatercept and 27 weeks for epoetin alfa, there were 301 patients included in the planned interim analysis.
The primary end point was transfusion independence for at least 12 weeks, alongside a mean hemoglobin increase of at least 15 g/dL within the first 24 weeks. At the time of the planned interim analysis, 58.5% of the luspatercept group (86 patients) had achieved the end point, compared with 31.2% (48 patients) of the epoetin alfa group (P < .0001).1
Secondary end points were as follows:
Patient Quality of Life. The potential to improve patient quality of life was not missed. Patients will not have to come to the clinic as often, Garcia-Manero said. “They will benefit from improved quality of life and better outcomes.”
“In patients with anemia with lower-risk MDS who depend on red blood cell transfusions, luspatercept almost doubles the number of people who achieve independence from transfusions for a period lasting 12 weeks or more, when compared with epoetin alfa, a current standard of care treatment,” ASCO expert Olatoyosi Odenike, MD, professor and director of the Leukemia Program, UChicago Medicine, said in a statement. "Luspatercept may be an effective first treatment option for anemia associated with lower-risk MDS.”2
According to study protocol, follow-up to 5 years is planned. Luspatercept is currently approved by the FDA for 2 indications:
On May 1, the FDA accepted Bristol Myers Squibb’s supplemental New Drug Application to broaden the indication to first-line treatment for patients with low-risk MDS. The target action date is August 23, 2023.5
Bristol Myers Squibb funded the study.
1. Garcia-Manero G, Platzbecker U, Santini V, et al. Efficacy and safety results from the COMMANDS trial: a phase 3 study evaluating luspatercept vs epoetin alfa in erythropoiesis-stimulating agent (ESA)naive transfusion-dependent (TD) patients (pts) with lowerrisk myelodysplastic syndromes (LR-MDS). J Clin Oncol. 2023;41(suppl 16): 7003. doi:10.1200/JCO.2023.41.16_suppl.7003
2. Luspatercept improves anemia and reduces reliance on blood transfusions for people with lower-risk myelodysplastic syndromes. News release. American Society of Clinical Oncology. May 25, 2023. Accessed June 25, 2023. https://old-prod.asco.org/about-asco/press-center/news-releases/luspatercept-improves-anemia-and-reduces-reliance-blood
3. Cristol H. Financial considerations for MDS. WebMD.com Reviewed December 29, 2022. Accessed June 25, 2023. https://www.webmd.com/cancer/lymphoma/financial-considerations-treating-mds
4. Carraway HE, Saygin C. Therapy for lower-risk MDS. Hematology Am Soc Hematol Educ Program. 2020;2020(1):426-433. doi:10.1182/hematology.2020000127
5. U.S. FDA accepts Priority Review for supplemental Biologics License Application and EMA validates application for Reblozyl (luspatercept-aamt) as first-line treatment of anemia in adults with lower-risk myelodysplastic syndromes (MDS). News release. Bristol Myers Squibb. May 1, 2023. Accessed June 25, 2023. https://bwnews.pr/43Y9dOe