Real-World Patient Characteristics, Treatment Patterns, and Outcomes in Patients with Lower-Risk Myelodysplastic Syndromes Who Have Been Treated with Luspatercept
Authors: Boccia Ralph , Xiao Hong , Miteva Dimana , Che Min , Gu Tao , McBride Ali , Glassberg Mrudula B. , Yucel Aylin 
Published: December 2023

Background: Myelodysplastic syndromes (MDS) are a group of rare, clonal bone marrow malignancies characterized by ineffective erythropoiesis. Erythropoiesis-stimulating agents (ESAs) are a treatment option for anemia in patients with lower-risk MDS (LR-MDS); however as only one in three patients respond to ESAs, there is a need for additional treatment options. In April 2020, luspatercept was approved for the treatment of anemia in adult patients with LR-MDS who failed to respond to ESAs. The aim of this study was to investigate real-world treatment patterns and early clinical outcomes in adult patients in the United States with LR-MDS receiving luspatercept.
Methods: This was a retrospective observational cohort study of adult patients (aged ≥ 18 years at initial MDS diagnosis) with an International Prognostic Scoring System/Revised IPSS (IPSS-R/IPSS) classification of Very Low-, Low-, or Intermediate-risk MDS on or before the initial MDS diagnosis date +30 days, who were actively treated with a therapy of interest (including ESAs, hypomethylating agents [HMAs], erythroid maturation agents [EMAs], iron chelation therapy [ICT], white blood cells [WBCs], growth factors, chemotherapy, immunomodulating drugs [IMiDs], and platelet growth factors), and who received at least one dose of luspatercept between initial MDS diagnosis and November 1, 2022 in the COTA Vantage database which contains longitudinal, HIPAA-compliant data pertaining to the diagnosis, clinical management, and outcomes of patients with cancer from a mix of academic and community settings. The index date was the date of luspatercept initiation. Patients were required to have at least 2 months of medical data post-index unless they died during this period. All analyses were descriptive.
Results: A total of 86 patients who were treated with luspatercept (median age 78.0 years, 79.1% White, 52.3% male, 80.2% ECOG 0-1) were included. Median baseline hemoglobin level was 7.8 g/dL (range: 5.3-11.4 g/dL). Median time from MDS diagnosis to luspatercept initiation was 35.4 months and the median follow-up time was 13.4 months. The majority of patients (89.5%) were previously treated with ESAs for a median duration of 9.0 months. The two most used ESAs were darbepoetin alfa (54.5%) and epoetin alfa (44.2%). In addition, 40.7% of patients had previously received a non-ESA treatment, most commonly azacitidine (62.9%) or lenalidomide (31.4%). The median duration of treatment (DoT) with luspatercept was 9.9 months. Around a quarter of patients who received luspatercept (25.6%, n = 22) received a further treatment, such as an ESA or an HMA for a median of 2.8 months. Overall, 51/76 (67.1%) patients with a baseline hemoglobin test who received luspatercept had an increase in hemoglobin of ≥1 g/dL compared with baseline (i.e. the closest hemoglobin test within 6 months prior to index date). Of these, 56.9% maintained the ≥1 g/dL hemoglobin level for ≥8 weeks and 45.1% maintained it for ≥16 weeks. Further, 44/76 (57.9%) patients with a baseline hemoglobin test who received luspatercept had an increase in hemoglobin ≥1.5 g/dL compared with baseline. Of these, 50.0% maintained the ≥1.5 g/dL hemoglobin level for ≥8 weeks and 25.0% maintained it for ≥16 weeks.
Conclusion: This real-world study described treatment patterns and outcomes in patients with LR-MDS receiving luspatercept. An improvement in hemoglobin levels was observed in more than half of patients. In a quarter of patients who had a ≥1.5 g/dL increase compared to baseline, these improvements were maintained for ≥16 weeks. As this was a relatively small and descriptive study, future analyses are required to further elucidate these findings.