ABSTRACT
Background: The EMA-approved, erythroid maturation agent, luspatercept, has been shown to decrease transfusion burden in patients with transfusion-dependent thalassemia (TDT). Aims: In this multicenter, retrospective cross-sectional study, real-world data from the use of luspatercept in TDT patients, managed in 5 major Thalassemia Centers in Greece are presented. Methods: Inclusion criteria included TDT patients, having received luspatercept as per approved indications for at least 3 months. Data cut-off date was 31/1/2022. We estimated the quantity of blood (in cc of Packed Red Blood Cells -PRBC) received over 12 weeks for the intervals: 12 weeks before starting treatment (baseline);1-12 weeks;5-16 weeks and 13-24 weeks post starting therapy. Changes in mean pre-transfusion hemoglobin (Hb), uric acid, creatinine, lactic acid dehydrogenase (LDH), white blood cells (WBC) and platelets counts were analyzed for these same respective periods. Adverse events (AE) were recorded. Statistical analysis performed with RStudio v.3.6.2. Results: Main results of the study are shown in Table 1. Forty-nine patients (median age: 46 years range:15-64, sex: M:F/33:16) received Luspatercept every 21 days. Data for weeks 5-16 and 13-24 were available for 30 and 16 patients, respectively. The initial dose of luspatercept was 1 mg/kg and increased selectively up to 1.25mg/kg based on tolerability and efficacy and according to guidelines. A statistically significant (p<0.005) decrease in PRBC transfused in all 12-weeks' intervals analyzed compared to baseline was observed. No statistically significant decrease of PRBC transfused was found between the intervals 5-16weeks and 13-24 weeks compared to the initial interval of 1-12 weeks. There was not a significant change for the mean pre-transfusion Hb compared to baseline. A statistically significant (p<0.005) increase in uric acid, creatinine, LDH , WBC and platelets was observed for the interval 1-12 weeks in comparison with baseline (mean: 6.42±1.64mg/dl vs 5.48±1.6mg/dl, 0.87±0.16mg/dl vs 0.83±0.18mg/dl, 352±205mg/dl vs 204±62mg/dl, 11.78x109 ±5.29x109/L vs 10.36x109±4.35x109/L, and 450x109±221x109/L vs 415x109±202x109/L, respectively. Similar difference was observed between the 13-24 weeks interval and baseline only for uric acid, LDH and platelets (mean: 6.28±1.41mg/dl vs 5.48±1.6mg/dl p=0.003, 406±301mg/dl vs 204±62mg/dl p=0.014, 467x109±226x109/L vs 415x109±202x109/L p<0.008 respectively). Twenty five out of 49 patients reported AE. The most common AE included bone pain 16/49 (32.6%) and fatigue 7/49 (14.2%). Frequent urination, headache, swelling at injection site, blurry vision, tearing, libido decrease, tachycardia, periorbital oedema, dizziness, and exacerbation of manic-depressive episodes were also reported. Twelve patients discontinued treatment. Reasons for discontinuation included: non-response to treatment (7 patients), adverse events (3 patients), non-compliance (1 patient), death due to COVID19 infection (1 patient). Summary/Conclusion: Real world data on the use of luspatercept in TDT parallel results from the trial, showing heterogeneous and lasting efficacy and acceptable toxicity. Longer follow up and increased number of patients are required to validate these initial observations. (Table Presented).