ABSTRACT
Background: An erythroid maturation agent, Luspatercept is approved to treat adults with β -thalassemia. Its availability in Greece coincided with severe blood shortages due to the COVID outbreak, making its administration even more necessary. Aims: Luspatarept's usage in patients with comorbidities. Methods: Between May and December 2021, luspatercept was administered for a period of 12 to 24 weeks to twelve individuals with confirmed β -thalassemia (β 0/β +: 4/12, β +/β +:3/12, β 0/β ++:1/12, β 0/β 0 :1/12,β +/β ++:1/12) and significant comorbidities such as chronic heart failure (3/12), osteoporosis (3/12), atrial fibrillation (2/12), extramedullary hematopoiesis (2/12) and cirrhosis (1/12). The average age was 48.3 years;7male /5 female. Prior to initiating luspatercept, the patient's medical history was reviewed for risk factors for thrombophilia (9/12 had low protein S and C and 2/12 had also low ATIII) as well as anticoagulant (4/12 on acenocoumarol) and antiplatelet (3/12 on aspirin ) medication related to splenectomy (10/12) or past thrombotic episodes (4/12).Transfusion requirements, transfusion intervals, mean hemoglobin and LDH values were documented for 12 weeks prior to and during luspatercept initiation. To maintain stable blood volumes in each transfusion, prestorage leukoreduced RBCs with an average volume per unit of 320 ml was used. Results: Table 1 summarizes the study's main results.Statistical significance is p <0.05. Throughout treatment, all but one patient (11/12) received a dose of 1 mg/kg. One patient did not respond to a dose increase of 1.25 g / kg and discontinued on week 12. Additionally, two other luspatercept responders discontinued treatment after the 12th and 24th week, respectively, due to significant fatigue. After 12 and 24 weeks, all patients who continued in luspatercept had a significant decrease in transfusion blood needs, approximately -29.4% and -36.1 % compared to baseline. They also showed significant increase in transfusion intervals for an average of 20.7 days. In addition, it became apparent that, although the volume of blood supplied was reduced and the interval between transfusions increased, the patients' hemoglobin levels remained adequately high in luspatercept treated patients. LDH as hemolysis biomarker, did not reveal any significant changes. During the follow-up period, no patient reported progression of existing comorbidities or the development of new ones. As far as their cardiovascular disease is concerned, the patients clinical status was stable NYHA II despite the reduction of transfusions. Six months after taking luspatercept, one patient showed an improvement in extramedullary hematopoiesis as evaluated by magnetic resonance imaging. Additionally, despite the presence of predisposing factors and the significant increase of platelets, no new thrombosis developed. Summary/Conclusion: In patients with significant comorbidities, luspatercept significantly decreased transfusion burden and prolonged transfusion intervals , without any observed worsening of their comorbidities or development of new ones. (Table Presented).
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).