Real-World Study Evaluates Luspatercept in MDS, Identifies Subgroups Most Likely to Benefit

By Cecilia Brown - Last Updated: June 13, 2023

A recent study showed luspatercept was “effective” for treating transfusion-dependent anemia in patients with myelodysplastic syndromes (MDS) outside of the clinical trial setting and identified subgroups of patients most likely to benefit from the therapy, according to its authors.

Researchers with Fondazione Italiana Sindromi Mielodisplastiche conducted a multicenter, observational trial to evaluate the efficacy and safety of luspatercept in a population of adults who received the treatment through a compassionate use program.

The study included adults who had MDS with ring sideroblasts according to 2016 World Health Organization criteria; met criteria for very low, low, or intermediate risk disease per the Revised International Prognostic Scoring System (IPSS-R); were receiving regular red blood cell transfusions; and were refractory or unlikely to respond to erythropoietin stimulating agents. Patients received luspatercept according to label instructions.

The study’s investigators replicated the statistical plan of the MEDALIST trial to evaluate luspatercept outside of a clinical trial. The primary endpoint was transfusion independence for at least eight weeks during weeks one through 24. The main secondary endpoints were transfusion independence for at least 12 weeks during weeks one through 24 and weeks one through 48.

The researchers screened 215 patients for enrollment, with 201 patients receiving at least one dose of luspatercept. The median patient age at enrollment was 74 years. Most patients (66.7%) had at least one comorbidity requiring ongoing treatment. The baseline transfusion burden was seven units over eight weeks. The median follow-up was 377 days.

Nearly one-third (30.8%) of patients achieved transfusion independence for at least eight weeks in the first 24 weeks, while 39.3% achieved transfusion independence for at least eight weeks in the first 48 weeks. The median longest duration of primary response was 23.9 weeks. Around one-third (35.3%) of patients achieved an erythroid response during the first 24 weeks of treatment.

Most patients (81.6%) received the maximum allowed dose of luspatercept 1.75 mg/kg at least once during the study period. The median dose of luspatercept at first transfusion independence response was 1.33 mg/kg.

The study’s investigators performed a multiple logistic regression analysis, finding a significant association between the baseline transfusion burden and the individual probability of achieving transfusion independence (P<.001). They did not find a correlation with age, sex, IPSS-R risk, time since initial diagnosis, or time since first red blood cell transfusion.

“The dose at first response was positively correlated with baseline transfusion burden,” the study’s authors wrote.

Serious adverse events occurred in 17.4% of patients. Cardiac events were the most common serious adverse events, occurring in 11 patients. A total of 20 patients died during the study, and five patients experienced evolution to acute myeloid leukemia (AML). All patients who experienced disease evolution to AML were still receiving luspatercept at the time of progression.

Nearly half (43.3%) of patients discontinued treatment during the study. Lack of benefit or loss of response, reported in 64.4% of patients who discontinued treatment, was the most common reason for discontinuation.

“In this study, we were able to confirm that luspatercept was effective for treating transfusion-dependent anemia outside the setting of a clinical trial and we observed that the benefit extended beyond the achievement of [transfusion independence], producing a significant reduction in the number of transfusions,” the study’s authors concluded. “Importantly, baseline transfusion burden can identify subgroups of patients with distinct probability to have a clinical benefit from the treatment.”


Lanino L, Restuccia F, Perego A, et al. Real-world efficacy and safety of luspatercept and predictive factors of response in patients with lower risk myelodysplastic syndromes with ring sideroblasts. Am J Hematol. 2023. doi:10.1002/ajh.26960

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