Safety, Efficacy of Luspatercept for MDS Confirmed in Real-World Setting

Patients with lower-risk myelodysplastic syndrome (LR-MDS) treated with luspatercept (Reblozyl; Celgene Corporation) after erythroid-stimulating agent (ESA) failure in a real-world setting experienced outcomes similar to those in the MEDALIST trial (NCT02631070), according to a new study published in the British Journal of Haematology.

Results from the phase 3 MEDALIST trial supported the FDA approval of luspatercept in 2020, with an initial indication for the treatment of certain adults with very low– to intermediate-risk MDS with anemia failing an ESA and requiring 2 or more red blood cell units over 8 weeks.² It was later approved as a first-line therapy for anemia in very low– to intermediate-risk MDS based on interim results from the phase 3 COMMANDS trial (NCT03682536).³

Even among patients with MDS and anemia with a high transfusion burden, 7 of 12 patients who responded experienced responses lasting longer than 6 months. | Image Credit: Eleni - stock.adobe.com

The new, retrospective study included 98 patients with LR-MDS who were transfusion-dependent after ESA failure and subsequently received luspatercept at 15 Greek and 2 Turkish sites.¹ Researchers aimed to assess the safety and efficacy of luspatercept in a real-world setting compared with clinical trials.

Patients with low- or intermediate-risk MDS were included in the study, and the median (5%-95% range) age was 75 (59-88) years. The median follow-up was 13.1 (4.2-39.8) months, and 54 patients had baseline next-generation sequencing panel mutational data available. Seventy-four patients received the maximum dose of luspatercept (1.75 mg/kg), 12 received an intermediate dose (1.33 mg/kg), and 12 received the minimum dose (1 mg/kg).

A total of 57 patients discontinued treatment, with 8 discontinuing due to adverse events, 8 due to death unrelated to treatment, 2 who proceeded to allogeneic stem cell transplantation, and 36 due to inadequate responses to luspatercept. The percentage of patients who discontinued treatment due to adverse events (8.2%) was similar to the rate reported in the MEDALIST study (8%), the authors noted. Three patients discontinued due to hemoglobin levels persistently higher than 11 g/dL.

Of 98 patients, 42 (42.9%) responded to treatment—12 of 48 (25%) in a high transfusion burden group, 21 of 37 (56.8%) in the intermediate transfusion burden group, and 9 of 13 (69.2%) in the low transfusion burden group (P = .002).

Among 88 patients who had 24 weeks of follow-up after luspatercept initiation, 39 (44.3%) experienced transfusion independence longer than 8 weeks. In the MEDALIST trial, 38% of patients experienced transfusion independence longer than 8 weeks, the authors noted, but the inclusion of patients with lower transfusion needs in their study could be the reason for these positive results.

All patients who responded to luspatercept did so within 8 months of initiation, with a median time to response of 3.7 (2-7.5) months, and many responses were long-lasting. The authors noted that in the high transfusion burden group, 7 of 12 patients who responded experienced responses lasting longer than 6 months. Additionally, responding to luspatercept and having less than 2 mutations were independent predictors of overall survival.

The study was limited by its retrospective nature and a lack of molecular data for a large proportion of patients, which limited the researchers’ ability to fully explore the impacts of genetic factors on outcomes. The median follow-up time was also relatively short.

“In summary, we have confirmed luspatercept's safety and efficacy in transfusion-dependent LR-MDS in the real-life setting,” the authors concluded. “Response rates are higher in lower transfusion-dependent patients, suggesting that early treatment initiation of luspatercept may be beneficial in LR-MDS patients.”

References

1. Bouchla A, Papageorgiou SG, Kotsianidis I, et al. Real-life experience of luspatercept in transfusion-dependent lower risk myelodysplastic syndrome patients. Br J Haematol. Published online May 5, 2025. doi:10.1111/bjh.20102

2. FDA approves luspatercept-aamt for anemia in adults with MDS. News release. FDA. April 6, 2020. Accessed May 22, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-luspatercept-aamt-anemia-adults-mds

3. Munz K. FDA approves luspatercept as first-line anemia treatment in patients with lower-risk MDS. AJMC^®. August 29, 2023. Accessed May 22, 2025. https://www.ajmc.com/view/fda-approves-luspatercept-as-first-line-anemia-treatment-in-patients-with-lower-risk-mds