Abstract
Background: In patients with lower-risk myelodysplastic syndrome (LR-MDS), luspatercept has demonstrated significant clinical benefit in treating transfusion-dependent (TD) anemia in randomized clinical trials. However, luspatercept's utilization patterns and associated clinical outcomes in treatment-naïve LR-MDS patients in real-world settings are not well documented. This study aimed to describe baseline characteristics, treatment patterns, and clinical outcomes in patients with LR-MDS treated with first-line (1L) luspatercept in France and Germany.
Methods: This retrospective study included adult patients diagnosed with LR-MDS who initiated 1L treatment with luspatercept for symptomatic or TD anemia, outside clinical trials. Medical record data were collected for patients treated after June 2020 in France and after May 2023 in Germany, with known ring sideroblast (RS) status at baseline. Data abstraction was led by participating hematologists/hemato-oncologists (N=39) from academic and community settings (charts were abstracted from December 2024-January 2025). The date of luspatercept therapy initiation defined the study index date. Patients were required to have ≥ 6 months of potential follow-up time from index date to the date of abstraction. Patients' baseline transfusion status was assessed during the 16-week preindex period and classified as non–transfusion-dependent (NTD) for 0 red blood cell (RBC) units and TD for > 0 RBC units (low transfusion burden [LTB], 1-7 units; high transfusion burden [HTB], ≥ 8 units). For TD patients, achieving transfusion independence (TI) (i.e., 0 RBC units) was the main outcome parameter and was assessed over any 12-week period during the first 6 months postindex. Hemoglobin (Hb) response (i.e., increase of ≥ 1.5 g/dL compared with the baseline Hb level) within 6 months of treatment initiation was also assessed. Time to discontinuation (TTD) and time to TI were analyzed using the Kaplan-Meier method. All analyses were descriptive.
Results: A total of 110 patients (53 in France and 57 in Germany) were included in the analysis (median age, 74 years; 54.5% male). Median follow-up was 13.1 months (first quartile [Q1], 10.1; third quartile [Q3], 22.4) from MDS diagnosis and 9.8 months (Q1, 7.4; Q3, 13.3) from luspatercept initiation. Among 106 patients with known transfusion status at baseline, 21 (19.8%) were NTD and 85 (80.2%) were TD (LTB, 54.1%; HTB, 45.9%). Median Hb level at baseline was 8.0 g/dL, and 60.9% were RS-positive (RS+). Median time to 1L luspatercept initiation from LR-MDS diagnosis was 1.6 months (Q1, 0.6; Q4, 5.6). Median TTD of luspatercept therapy was 25.3 months (95% confidence interval [CI], 19.4-not estimable); the estimated proportion of patients who remained on therapy at 12 and 24 months was 68.4% and 57.9%, respectively. Among those who discontinued (n=33), the majority (54.5% [n=18]) had their dose at discontinuation at or below 1.33 mg/dL; among these patients who were alive (n=13/18), the most frequent reasons for discontinuation (not mutually exclusive) were lack of efficacy (5/13), patient decision (5/13), progressive disease (3/13), or adverse event (2/13). Among baseline TD patients (with non-missing outcome data, n=81), 64.2% achieved 12-week TI within 6 months; the rate of TI achievement within 6 months was 68.8% in RS+ patients and 57.6% in RS-negative (RS–) patients. Median time to TI among TD patients (n=81) was 2.4 months (95% CI, 1.6-3.1). Among all patients with non-missing Hb outcome data (n=98), an Hb increase of ≥ 1.5 g/dL was observed in 53.1% (RS+, 51.7% [31/60]; RS–, 55.3% [21/38]). Among NTD patients with non-missing Hb outcome data (n=17/21), an Hb increase of ≥ 1.5 g/dL was observed in 64.7% (RS+, 61.5% [8/13]; RS–, 75.0% [3/4]).Conclusions: In this retrospective study, patients with LR-MDS treated with 1L luspatercept showed substantial clinical response with high rates of TI achievement and Hb response during the first 6 months after treatment initiation, regardless of RS status. Most patients continued with the luspatercept therapy for over a year, and among those who discontinued, a considerable proportion discontinued before reaching the optimal, recommended target dose of 1.75 mg/kg despite citing lack of efficacy as one of the top reasons for discontinuation. Overall, these findings complement efficacy data from clinical trials and highlight the real-world effectiveness of 1L treatment with luspatercept in LR-MDS.
