LUSPATERCEPT DECREASES TRANSFUSION BURDEN AND LIVER IRON CONCENTRATION IN REGULARLY TRANSFUSED ADULTS WITH BETA-THALASSEMIA
(Abstract release date: 05/19/16)
EHA Library. Piga A. 06/12/16; 135330; S836
Dr. Antonio Piga
Contributions
Contributions
Abstract
Abstract: S836
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:45 - 09:00
Location: Room H6
Background
Luspatercept (ACE-536), a fusion protein containing a modified activin receptor type IIB, is being developed for the treatment of β-thalassemia. Luspatercept binds to GDF11 and other ligands in the TGF-β superfamily to promote late-stage erythroid differentiation. Luspatercept corrected the effects of ineffective erythropoiesis in a thalassemia mouse model (Suragani R, Blood 2014) and was well tolerated and increased hemoglobin in a phase 1 clinical study (Attie K, Am J Hematol 2014).
Aims
This is an ongoing, phase 2, multicenter, open-label, dose-finding study followed by a long-term extension study to evaluate the effects of luspatercept in adults with β-thalassemia, including a subgroup on regular transfusions (≥4 units RBC/8 weeks). Endpoints included RBC transfusion burden (units/12 weeks), liver iron concentration (LIC) by MRI, safety, and quality of life questionnaires.
Methods
Inclusion criteria included age ≥18 yr and genetic confirmation of β-thalassemia. Luspatercept was administered SC every 3 wks for up to 5 doses in the dose-ranging study (completed) with a 2-month follow-up unless enrolled directly into a 2-year extension study (ongoing). Six sequential cohorts (n=35 total) were treated at escalating doses from 0.2 to 1.25 mg/kg. An additional expansion cohort (n=29) was treated with a starting dose of 0.8 mg/kg with escalation up to 1.25 mg/kg. Of the 64 patients (pts) treated in the dose-ranging study (including 30 pts regularly transfused), 51 enrolled in the extension study. RBC transfusions during the study were administered based on each patient’s usual pre-transfusion hemoglobin threshold.
Results
Data (as of 25 Sept 2015) were evaluable for 28 of 30 pts on regular RBC transfusions. Median age was 37.5 yr, ranging from 21 to 54 yr, and 57.1% had prior splenectomy. At baseline, median transfusion burden was 8 units/12 weeks (range 4-18 units). Mean (±SD) LIC was 4.5 ± 4.6 mg/g dw. 27 pts were on iron chelation therapy (ICT) at baseline.21/28 (75%) pts achieved ≥33% decrease and 16/28 (57%) achieved ≥50% decrease in transfusion burden over any 12-week period compared with the 12 weeks prior to treatment (mean decrease was 56% in 23 pts with at least 12 weeks on study). 4/8 (50%) pts with baseline LIC ≥5 mg/g dw had a decrease in LIC ≥2 mg/g dw (mean decrease 3.1 mg/g dw, 35.1%) during the 16-week base study; 14/14 (100%) pts with baseline LIC <5 mg/g dw maintained LIC <5 mg/g dw.Luspatercept was generally well tolerated, with no related serious adverse events reported to date. Adverse events in this regularly transfused subgroup were mostly mild-moderate and the most frequent related adverse events (≥4 pts) were bone pain, myalgia, arthralgia, headache, asthenia, and musculoskeletal pain.
Conclusion
Luspatercept treatment was well-tolerated and led to decreased RBC transfusion requirements in regularly transfused patients with β-thalassemia. The decrease in RBC transfusions correlated with decreases in liver iron concentration. These changes represent a significant reduction in disease burden for regularly transfused patients with β-thalassemia. A Phase 3 study of luspatercept in adults who require regular RBC transfusions due to β-thalassemia is ongoing (BELIEVE study; clinicaltrials.gov NCT02604433).
Session topic: Transfusion Medicine
Keyword(s): Clinical trial, Erythropoieisis, TGF-, Thalassemia
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:45 - 09:00
Location: Room H6
Background
Luspatercept (ACE-536), a fusion protein containing a modified activin receptor type IIB, is being developed for the treatment of β-thalassemia. Luspatercept binds to GDF11 and other ligands in the TGF-β superfamily to promote late-stage erythroid differentiation. Luspatercept corrected the effects of ineffective erythropoiesis in a thalassemia mouse model (Suragani R, Blood 2014) and was well tolerated and increased hemoglobin in a phase 1 clinical study (Attie K, Am J Hematol 2014).
Aims
This is an ongoing, phase 2, multicenter, open-label, dose-finding study followed by a long-term extension study to evaluate the effects of luspatercept in adults with β-thalassemia, including a subgroup on regular transfusions (≥4 units RBC/8 weeks). Endpoints included RBC transfusion burden (units/12 weeks), liver iron concentration (LIC) by MRI, safety, and quality of life questionnaires.
Methods
Inclusion criteria included age ≥18 yr and genetic confirmation of β-thalassemia. Luspatercept was administered SC every 3 wks for up to 5 doses in the dose-ranging study (completed) with a 2-month follow-up unless enrolled directly into a 2-year extension study (ongoing). Six sequential cohorts (n=35 total) were treated at escalating doses from 0.2 to 1.25 mg/kg. An additional expansion cohort (n=29) was treated with a starting dose of 0.8 mg/kg with escalation up to 1.25 mg/kg. Of the 64 patients (pts) treated in the dose-ranging study (including 30 pts regularly transfused), 51 enrolled in the extension study. RBC transfusions during the study were administered based on each patient’s usual pre-transfusion hemoglobin threshold.
Results
Data (as of 25 Sept 2015) were evaluable for 28 of 30 pts on regular RBC transfusions. Median age was 37.5 yr, ranging from 21 to 54 yr, and 57.1% had prior splenectomy. At baseline, median transfusion burden was 8 units/12 weeks (range 4-18 units). Mean (±SD) LIC was 4.5 ± 4.6 mg/g dw. 27 pts were on iron chelation therapy (ICT) at baseline.21/28 (75%) pts achieved ≥33% decrease and 16/28 (57%) achieved ≥50% decrease in transfusion burden over any 12-week period compared with the 12 weeks prior to treatment (mean decrease was 56% in 23 pts with at least 12 weeks on study). 4/8 (50%) pts with baseline LIC ≥5 mg/g dw had a decrease in LIC ≥2 mg/g dw (mean decrease 3.1 mg/g dw, 35.1%) during the 16-week base study; 14/14 (100%) pts with baseline LIC <5 mg/g dw maintained LIC <5 mg/g dw.Luspatercept was generally well tolerated, with no related serious adverse events reported to date. Adverse events in this regularly transfused subgroup were mostly mild-moderate and the most frequent related adverse events (≥4 pts) were bone pain, myalgia, arthralgia, headache, asthenia, and musculoskeletal pain.
Conclusion
Luspatercept treatment was well-tolerated and led to decreased RBC transfusion requirements in regularly transfused patients with β-thalassemia. The decrease in RBC transfusions correlated with decreases in liver iron concentration. These changes represent a significant reduction in disease burden for regularly transfused patients with β-thalassemia. A Phase 3 study of luspatercept in adults who require regular RBC transfusions due to β-thalassemia is ongoing (BELIEVE study; clinicaltrials.gov NCT02604433).
Session topic: Transfusion Medicine
Keyword(s): Clinical trial, Erythropoieisis, TGF-, Thalassemia
Abstract: S836
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:45 - 09:00
Location: Room H6
Background
Luspatercept (ACE-536), a fusion protein containing a modified activin receptor type IIB, is being developed for the treatment of β-thalassemia. Luspatercept binds to GDF11 and other ligands in the TGF-β superfamily to promote late-stage erythroid differentiation. Luspatercept corrected the effects of ineffective erythropoiesis in a thalassemia mouse model (Suragani R, Blood 2014) and was well tolerated and increased hemoglobin in a phase 1 clinical study (Attie K, Am J Hematol 2014).
Aims
This is an ongoing, phase 2, multicenter, open-label, dose-finding study followed by a long-term extension study to evaluate the effects of luspatercept in adults with β-thalassemia, including a subgroup on regular transfusions (≥4 units RBC/8 weeks). Endpoints included RBC transfusion burden (units/12 weeks), liver iron concentration (LIC) by MRI, safety, and quality of life questionnaires.
Methods
Inclusion criteria included age ≥18 yr and genetic confirmation of β-thalassemia. Luspatercept was administered SC every 3 wks for up to 5 doses in the dose-ranging study (completed) with a 2-month follow-up unless enrolled directly into a 2-year extension study (ongoing). Six sequential cohorts (n=35 total) were treated at escalating doses from 0.2 to 1.25 mg/kg. An additional expansion cohort (n=29) was treated with a starting dose of 0.8 mg/kg with escalation up to 1.25 mg/kg. Of the 64 patients (pts) treated in the dose-ranging study (including 30 pts regularly transfused), 51 enrolled in the extension study. RBC transfusions during the study were administered based on each patient’s usual pre-transfusion hemoglobin threshold.
Results
Data (as of 25 Sept 2015) were evaluable for 28 of 30 pts on regular RBC transfusions. Median age was 37.5 yr, ranging from 21 to 54 yr, and 57.1% had prior splenectomy. At baseline, median transfusion burden was 8 units/12 weeks (range 4-18 units). Mean (±SD) LIC was 4.5 ± 4.6 mg/g dw. 27 pts were on iron chelation therapy (ICT) at baseline.21/28 (75%) pts achieved ≥33% decrease and 16/28 (57%) achieved ≥50% decrease in transfusion burden over any 12-week period compared with the 12 weeks prior to treatment (mean decrease was 56% in 23 pts with at least 12 weeks on study). 4/8 (50%) pts with baseline LIC ≥5 mg/g dw had a decrease in LIC ≥2 mg/g dw (mean decrease 3.1 mg/g dw, 35.1%) during the 16-week base study; 14/14 (100%) pts with baseline LIC <5 mg/g dw maintained LIC <5 mg/g dw.Luspatercept was generally well tolerated, with no related serious adverse events reported to date. Adverse events in this regularly transfused subgroup were mostly mild-moderate and the most frequent related adverse events (≥4 pts) were bone pain, myalgia, arthralgia, headache, asthenia, and musculoskeletal pain.
Conclusion
Luspatercept treatment was well-tolerated and led to decreased RBC transfusion requirements in regularly transfused patients with β-thalassemia. The decrease in RBC transfusions correlated with decreases in liver iron concentration. These changes represent a significant reduction in disease burden for regularly transfused patients with β-thalassemia. A Phase 3 study of luspatercept in adults who require regular RBC transfusions due to β-thalassemia is ongoing (BELIEVE study; clinicaltrials.gov NCT02604433).
Session topic: Transfusion Medicine
Keyword(s): Clinical trial, Erythropoieisis, TGF-, Thalassemia
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:45 - 09:00
Location: Room H6
Background
Luspatercept (ACE-536), a fusion protein containing a modified activin receptor type IIB, is being developed for the treatment of β-thalassemia. Luspatercept binds to GDF11 and other ligands in the TGF-β superfamily to promote late-stage erythroid differentiation. Luspatercept corrected the effects of ineffective erythropoiesis in a thalassemia mouse model (Suragani R, Blood 2014) and was well tolerated and increased hemoglobin in a phase 1 clinical study (Attie K, Am J Hematol 2014).
Aims
This is an ongoing, phase 2, multicenter, open-label, dose-finding study followed by a long-term extension study to evaluate the effects of luspatercept in adults with β-thalassemia, including a subgroup on regular transfusions (≥4 units RBC/8 weeks). Endpoints included RBC transfusion burden (units/12 weeks), liver iron concentration (LIC) by MRI, safety, and quality of life questionnaires.
Methods
Inclusion criteria included age ≥18 yr and genetic confirmation of β-thalassemia. Luspatercept was administered SC every 3 wks for up to 5 doses in the dose-ranging study (completed) with a 2-month follow-up unless enrolled directly into a 2-year extension study (ongoing). Six sequential cohorts (n=35 total) were treated at escalating doses from 0.2 to 1.25 mg/kg. An additional expansion cohort (n=29) was treated with a starting dose of 0.8 mg/kg with escalation up to 1.25 mg/kg. Of the 64 patients (pts) treated in the dose-ranging study (including 30 pts regularly transfused), 51 enrolled in the extension study. RBC transfusions during the study were administered based on each patient’s usual pre-transfusion hemoglobin threshold.
Results
Data (as of 25 Sept 2015) were evaluable for 28 of 30 pts on regular RBC transfusions. Median age was 37.5 yr, ranging from 21 to 54 yr, and 57.1% had prior splenectomy. At baseline, median transfusion burden was 8 units/12 weeks (range 4-18 units). Mean (±SD) LIC was 4.5 ± 4.6 mg/g dw. 27 pts were on iron chelation therapy (ICT) at baseline.21/28 (75%) pts achieved ≥33% decrease and 16/28 (57%) achieved ≥50% decrease in transfusion burden over any 12-week period compared with the 12 weeks prior to treatment (mean decrease was 56% in 23 pts with at least 12 weeks on study). 4/8 (50%) pts with baseline LIC ≥5 mg/g dw had a decrease in LIC ≥2 mg/g dw (mean decrease 3.1 mg/g dw, 35.1%) during the 16-week base study; 14/14 (100%) pts with baseline LIC <5 mg/g dw maintained LIC <5 mg/g dw.Luspatercept was generally well tolerated, with no related serious adverse events reported to date. Adverse events in this regularly transfused subgroup were mostly mild-moderate and the most frequent related adverse events (≥4 pts) were bone pain, myalgia, arthralgia, headache, asthenia, and musculoskeletal pain.
Conclusion
Luspatercept treatment was well-tolerated and led to decreased RBC transfusion requirements in regularly transfused patients with β-thalassemia. The decrease in RBC transfusions correlated with decreases in liver iron concentration. These changes represent a significant reduction in disease burden for regularly transfused patients with β-thalassemia. A Phase 3 study of luspatercept in adults who require regular RBC transfusions due to β-thalassemia is ongoing (BELIEVE study; clinicaltrials.gov NCT02604433).
Session topic: Transfusion Medicine
Keyword(s): Clinical trial, Erythropoieisis, TGF-, Thalassemia
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