Contributions
Abstract: EP1305
Type: E-Poster Presentation
Session title: Thalassemias
Background
β-thalassemia is a hereditary anemia characterized by ineffective erythropoiesis. Luspatercept binds to selected TGF-β superfamily ligands, reducing aberrant Smad2/3 signaling and promoting late-stage erythroid maturation. Luspatercept is approved by the EMA and FDA for the treatment of adult patients (pts) with transfusion-dependent (TD) β-thalassemia. In a phase 2 study in pts with either TD or non-transfusion dependent (NTD) β-thalassemia, luspatercept increased hemoglobin (Hb) levels in NTD pts, reduced transfusion burden in TD pts, was well tolerated (Piga et al., Blood 2019;133(12):1279–89), and allowed the design of a 5-yr extension study.
Aims
To evaluate long-term efficacy and safety in pts enrolled in the phase 2 open-label study of luspatercept in β‑thalassemia.
Methods
Eligible pts were ≥18 yrs old and either NTD (<4 red blood cell [RBC] U/8 wks prior to first dose with baseline Hb <10 g/dL) or TD (≥4 RBC U/8 wks prior to first dose, confirmed over 6 months). Pts received luspatercept for up to 3 months in the base study (NCT01749540); pts were then eligible for treatment for up to 5 additional yrs in the extension study at a starting dose of 0.8 mg/kg (with dose titration up to 1.25 mg/kg) every 3 wks subcutaneously (NCT02268409).
Results
As of 18 June 2020, 51 (80%) of the 64 pts from the base study continued onto the extension study. Of the 51 pts, 27 were NTD and 24 TD; median (range) age was 37 (22–62) yrs; 62.7% had prior splenectomy. For NTD pts, at baseline, median (range) Hb was 8.65 (7.6–9.8) g/dL; mean (SD) serum ferritin was 635.1 (387.3) µg/L. For TD pts, at baseline, median (range) transfusion burden was 8 (4–15) U/12 wks; mean (SD) serum ferritin was 1011.6 (795.5) µg/L.
Of the 27 NTD pts, 21 (78%) achieved a mean Hb increase ≥1.0 g/dL, and 17 (63%) achieved a mean Hb increase ≥1.5 g/dL over any 12 wks vs baseline. Mean Hb increase in NTD pts exceeded 1.0 g/dL by Wk 6 and was sustained throughout the extension study (Figure); mean (SD) duration of consecutive 12-wk periods of response was 1147.0 (637.5) days. Improvement in FACIT-Fatigue score in NTD pts correlated with change in Hb level at Wk 24 (r=0.71, P=0.0015). Improvement in 6-minute walk distance in NTD pts trended with change in Hb level at Wk 48 (r=0.64, P=0.0658).
Of the 24 TD pts, 20 (83%) achieved a ≥33% reduction in transfusion burden over any 12-wk interval vs baseline; mean (SD) duration of consecutive 12-wk periods of response was 462.5 (579.9) days. 12/24 (50%) TD pts achieved ≥33% reduction in transfusion burden over a fixed 12-wk interval (Wks 13–24) compared to baseline, and 8/24 (33%) responded during Wks 37–48. There was a trend for decreased mean serum ferritin levels from baseline for NTD and TD pts treated in the extension study which was maintained at Wk 252 (4.8 yrs after start).
Luspatercept had a tolerable safety profile across all pts in the extension study; 1 (2%) pt experienced a serious adverse event (AE) related to study drug (grade 3 biliary colic) and 5 (10%) pts experienced treatment-emergent AEs leading to study discontinuation (1 pt each: hemolytic anemia, musculoskeletal cerebrovascular accident, paresthesia, priapism, and pulmonary embolism).
Conclusion
In this assessment of longer-term outcomes in pts with β-thalassemia, luspatercept treatment was associated with sustained increases in Hb levels in NTD pts, and sustained decreases in transfusion burden in TD pts. There was a trend for a decrease in mean serum ferritin levels in NTD and TD pts. Luspatercept was associated with a tolerable safety profile over the extended observation period.
Keyword(s): Beta thalassemia, Clinical trial
Abstract: EP1305
Type: E-Poster Presentation
Session title: Thalassemias
Background
β-thalassemia is a hereditary anemia characterized by ineffective erythropoiesis. Luspatercept binds to selected TGF-β superfamily ligands, reducing aberrant Smad2/3 signaling and promoting late-stage erythroid maturation. Luspatercept is approved by the EMA and FDA for the treatment of adult patients (pts) with transfusion-dependent (TD) β-thalassemia. In a phase 2 study in pts with either TD or non-transfusion dependent (NTD) β-thalassemia, luspatercept increased hemoglobin (Hb) levels in NTD pts, reduced transfusion burden in TD pts, was well tolerated (Piga et al., Blood 2019;133(12):1279–89), and allowed the design of a 5-yr extension study.
Aims
To evaluate long-term efficacy and safety in pts enrolled in the phase 2 open-label study of luspatercept in β‑thalassemia.
Methods
Eligible pts were ≥18 yrs old and either NTD (<4 red blood cell [RBC] U/8 wks prior to first dose with baseline Hb <10 g/dL) or TD (≥4 RBC U/8 wks prior to first dose, confirmed over 6 months). Pts received luspatercept for up to 3 months in the base study (NCT01749540); pts were then eligible for treatment for up to 5 additional yrs in the extension study at a starting dose of 0.8 mg/kg (with dose titration up to 1.25 mg/kg) every 3 wks subcutaneously (NCT02268409).
Results
As of 18 June 2020, 51 (80%) of the 64 pts from the base study continued onto the extension study. Of the 51 pts, 27 were NTD and 24 TD; median (range) age was 37 (22–62) yrs; 62.7% had prior splenectomy. For NTD pts, at baseline, median (range) Hb was 8.65 (7.6–9.8) g/dL; mean (SD) serum ferritin was 635.1 (387.3) µg/L. For TD pts, at baseline, median (range) transfusion burden was 8 (4–15) U/12 wks; mean (SD) serum ferritin was 1011.6 (795.5) µg/L.
Of the 27 NTD pts, 21 (78%) achieved a mean Hb increase ≥1.0 g/dL, and 17 (63%) achieved a mean Hb increase ≥1.5 g/dL over any 12 wks vs baseline. Mean Hb increase in NTD pts exceeded 1.0 g/dL by Wk 6 and was sustained throughout the extension study (Figure); mean (SD) duration of consecutive 12-wk periods of response was 1147.0 (637.5) days. Improvement in FACIT-Fatigue score in NTD pts correlated with change in Hb level at Wk 24 (r=0.71, P=0.0015). Improvement in 6-minute walk distance in NTD pts trended with change in Hb level at Wk 48 (r=0.64, P=0.0658).
Of the 24 TD pts, 20 (83%) achieved a ≥33% reduction in transfusion burden over any 12-wk interval vs baseline; mean (SD) duration of consecutive 12-wk periods of response was 462.5 (579.9) days. 12/24 (50%) TD pts achieved ≥33% reduction in transfusion burden over a fixed 12-wk interval (Wks 13–24) compared to baseline, and 8/24 (33%) responded during Wks 37–48. There was a trend for decreased mean serum ferritin levels from baseline for NTD and TD pts treated in the extension study which was maintained at Wk 252 (4.8 yrs after start).
Luspatercept had a tolerable safety profile across all pts in the extension study; 1 (2%) pt experienced a serious adverse event (AE) related to study drug (grade 3 biliary colic) and 5 (10%) pts experienced treatment-emergent AEs leading to study discontinuation (1 pt each: hemolytic anemia, musculoskeletal cerebrovascular accident, paresthesia, priapism, and pulmonary embolism).
Conclusion
In this assessment of longer-term outcomes in pts with β-thalassemia, luspatercept treatment was associated with sustained increases in Hb levels in NTD pts, and sustained decreases in transfusion burden in TD pts. There was a trend for a decrease in mean serum ferritin levels in NTD and TD pts. Luspatercept was associated with a tolerable safety profile over the extended observation period.
Keyword(s): Beta thalassemia, Clinical trial