New Real-World Data Analysis: Luspatercept for Lower-Risk MDS Anemia

A retrospective analysis of real-world data found that management for anemia in heavily-pretreated, lower-risk myelodysplastic syndromes (MDS) with luspatercept brings high rates of durable transfusion independence. A team of researchers lead by Marisa Kometas, MD, of the UT Southwestern Medical Center in Dallas, Texas, presented these results at the Twelfth Annual Meeting of the Society of Hematologic Oncology.

The analysis encompassed 37 patients with lower-risk MDS treated with luspatercept at an academic tertiary referral center from January 2020 to December 2023. The baseline patient characteristics of interest included prior therapies received, ring sideroblast status, karyotype, gene mutations, and transfusion burden.

Among 31 patients with evaluable response data, 52% achieved erythroid hematologic improvement; 22% of the patients who responded eventually lost transfusion independence, but in 50% of these it was restored following luspatercept dose increases.

Dr. Kometas and colleagues observed that luspatercept response was associated with baseline serum erythropoietin levels below 100 mU/mL (P=.02), but not with baseline transfusion burden. Moreover, luspatercept doses of 1.00, 1.33, and 1.75 mg/kg yielded equal rates of transfusion independence.

Regarding the durations of transfusion independence achieved, 48% of transfusion-dependent patients achieved 16 or more weeks of independence and the median duration of transfusion independence was 48 weeks. Response did not differ significantly between patients who had high or low baseline transfusion burden.

“As luspatercept gains prominence as first-line therapy, further investigation is required to define predictors of response,” Dr. Kometas and colleagues commented.

The research team reported that adverse effects included shortness of breath, falls, fatigue, and hypertension, and led to discontinuation in 8% of patients. Overall, 11% of patients progressed to high-risk MDS or to acute myeloid leukemia. Median leukemia-free overall survival was not reached and did not differ between responders and non-responders.

Reference

Kometas M, Hyak J, Hoff F, et al. Real world efficacy of luspatercept in patients with lower-risk myelodysplastic syndromes/neoplasms (LR-MDS); a single center study in a heavily pretreated cohort. Abstract #MDS-199. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; September 4-7, 2024; Houston, Texas.