EFFICACY
Reduce or eliminate transfusions
The efficacy of Reblozyl in MDS is based on the double-blind, randomized, placebo-controlled, phase 3 MEDALIST trial (with 153 patients treated with Reblozyl and 76 patients receiving placebo).1
Significantly more patients experienced RBC transfusion independence (TI) with Reblozyl vs placebo.1
- 37.9% achieved TI for at least 8 weeks (vs placebo 13.2%, P<0.0001) during Weeks 1-241
Primary Endpoint: RBC transfusion independence (TI)
≥8 weeks • Weeks 1-241
Significantly more patients experienced RBC-TI with Reblozyl vs placebo1
Significantly more patients on Reblozyl experienced a longer RBC-TI period vs placebo.1
- 28.1% achieved TI for at least 12 weeks (vs placebo 7.9%, P=0.0002) during Weeks 1-241
- 33.3% achieved TI for at least 12 weeks (vs placebo 11.8%, P=0.0003) during Weeks 1-481
Secondary Endpoint: RBC-TI ≥12 weeks • Weeks 1-481
Significantly more patients experienced a longer RBC-TI period with Reblozyl vs placebo1
Patients receiving Reblozyl had fewer RBC transfusion events vs placebo during Weeks 1-24 and Weeks 25-481
During Weeks 1-24:
- With Reblozyl, patients had 6.26 transfusion events vs 9.20 with placebo (0.68 relative risk vs placebo)1
During Weeks 25-48:
- With Reblozyl, patients had 6.27 transfusion events vs 8.72 with placebo (0.72 relative risk vs placebo)1
Secondary Endpoint: RBC transfusion event frequency • Weeks 1-241
Fewer events with Reblozly vs placebo
Patients receiving Reblozyl required fewer RBC transfusion units vs placebo during Weeks 1-24 and Weeks 25-48 1
During Weeks 1-24:
- Of patients with a low baseline transfusion burden (<6 units/8 weeks), those receiving Reblozyl received 7.2 units vs 12.8 units with placebo
- Of patients with a high baseline transfusion burden (≥6 units/8 weeks), those receiving Reblozyl received 18.9 units vs 23.7 units with placebo
During Weeks 25-48:
- Of patients with a low baseline transfusion burden (<6 units/8 weeks), those receiving Reblozyl received 7.5 units vs 11.8 units with placebo
- Of patients with a high baseline transfusion burden (≥6 units/8 weeks), those receiving Reblozyl received 19.6 units vs 22.9 units with placebo
Secondary Endpoint: RBC transfusion units • Weeks 1-241
Fewer RBC transfusion units with Reblozyl vs placebo
Low baseline transfusion
burden (<6 units/8 weeks)
High baseline transfusion
burden (≥6 units/8 weeks)
Reduce or eliminate transfusions
Erythroid maturation for significant red blood cell (RBC) transfusion reduction
Primary Endpoint: RBC transfusion independence (TI) ≥8 weeks • Weeks 1-241
Significantly more patients experienced RBC-TI with Reblozyl vs placebo1
The efficacy of Reblozyl in MDS is based on the double-blind, randomized, placebo-controlled, phase 3 MEDALIST trial (with 153 patients treated with Reblozyl and 76 patients receiving placebo).1
Secondary Endpoints
Secondary Endpoint: RBC-TI ≥12 weeks • Weeks 1-481
Significantly more patients experienced a longer RBC-TI period with Reblozyl vs placebo1
- 28.1% achieved TI for at least 12 weeks (vs placebo 7.9%, P=0.0002) during Weeks 1-241
- 33.3% achieved TI for at least 12 weeks (vs placebo 11.8%, P=0.0003) during Weeks 1-481
Secondary Endpoint: RBC transfusion event frequency • Weeks 1-241
Patients receiving Reblozyl had fewer RBC transfusion events vs placebo during Weeks 1-24 and Weeks 25-481
During Weeks 1-24:
- With Reblozyl, patients had 6.26 transfusion events vs 9.20 with placebo (0.68 relative risk vs placebo)1
During Weeks 25-48:
- With Reblozyl, patients had 6.27 transfusion events vs 8.72 with placebo (0.72 relative risk vs placebo)1
Secondary Endpoint: RBC transfusion units • Weeks 1-241
Patients receiving Reblozyl required fewer RBC transfusion units vs placebo during Weeks 1-24 and Weeks 25-48 1
Low baseline transfusion burden (<6 units/8 weeks)
High baseline transfusion burden (≥6 units/8 weeks)
During Weeks 1-24:
- Of patients with a low baseline transfusion burden (<6 units/8 weeks), those receiving Reblozyl received 7.2 units vs 12.8 units with placebo
- Of patients with a high baseline transfusion burden (≥6 units/8 weeks), those receiving Reblozyl received 18.9 units vs 23.7 units with placebo
During Weeks 25-48:
- Of patients with a low baseline transfusion burden (<6 units/8 weeks), those receiving Reblozyl received 7.5 units vs 11.8 units with placebo
- Of patients with a high baseline transfusion burden (≥6 units/8 weeks), those receiving Reblozyl received 19.6 units vs 22.9 units with placebo
The efficacy and safety outcomes for Reblozyl were evaluated
in the pivotal phase 3 MEDALIST trial1-3
MEDALIST (ACE-536-MDS-001) was a global, randomized, double-blind, placebo-controlled Phase 3 trial involving adult patients with anemia requiring RBC transfusions (≥2 units/8 weeks) due to IPSS-R very low-, low-, or intermediate-risk MDS, who have RS (with either ≥15% ring sideroblasts or ≥5% ring sideroblasts if an SF3B1 mutation was present). Patients were required to have either received prior treatment with an ESA with inadequate response, to be ineligible for ESAs (determined to be unlikely to respond to ESA treatment with serum EPO >200 U/L), or intolerant to ESA treatment.1
Primary endpoint: RBC transfusion independence (RBC-TI) ≥8 weeks (Weeks 1-24)1
References: 1. Reblozyl® (luspatercept) Summary of Product Characteristics (SmPC). Celgene 2020. 2. Fenaux P, Haase D, Sanz GF, Santini V, Buske C; on behalf of the ESMO Guidelines Working Group. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(suppl 3):iii57-iii69. 3. Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382:140-151.
The efficacy and safety outcomes for Reblozyl were evaluated in the pivotal Phase 3 MEDALIST trial1,2
MEDALIST (ACE-536-MDS-001) was a global, randomized, double-blind, placebo-controlled Phase 3 trial involving adult patients with anemia requiring RBC transfusions (≥2 units/8 weeks) due to IPSS-R very low-, low-, or intermediate-risk MDS, who have RS (with either ≥15% ring sideroblasts or ≥5% ring sideroblasts if an SF3B1 mutation was present). Patients were required to have either received prior treatment with an ESA with inadequate response, to be ineligible for ESAs (determined to be unlikely to respond to ESA treatment with serum EPO >200 U/L), or intolerant to ESA treatment.1
Primary endpoint: RBC transfusion independence (RBC-TI) ≥8 weeks (Weeks 1-24)1
References:
1. Reblozyl® (luspatercept) Summary of Product Characteristics (SmPC). Celgene 2020.
2. Fenaux P, Platzbecker, GJ, Mufti G et al. Luspatercept patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382:149-151.
Improve hemoglobin levels
More patients on Reblozyl achieved a hematologic improvement, according to the International Working Group (IWG) 2006 response criteria, during Weeks 1-24.1,2
During Weeks 1-24:
- 52.9% of patients achieved modified hematologic improvement-erythroid (mHI-E) vs 11.8% for placebo1,c
- 63.0% achieved a mean hemoglobin (Hb) increase of at least 1.5 g/dL for 8 weeks vs 5.0% for placebo1,c
- 48.6% achieved a RBC transfusion reduction of 4 units/8 weeks vs 14.3% for placebo1,c
Exploratory Endpoint: Modified hematologic improvement-erythroid (mHI-E)a,b,c • Weeks 1-241
More patients achieved mHI-E at Week 24 with Reblozyl vs placebo1
aResponse criteria were developed by the IWG.
bThe proportion of patients meeting the HI-E criteria as per IWG 2006 criteria sustained over a consecutive 56-day period during the indicated treatment period.
cIn patients with a baseline transfusion burden of ≥4 units/8 weeks, mHI-E was defined as a reduction in RBC transfusions of at least 4 units/8 weeks. For patients with a baseline RBC burden of <4 units/8 weeks, mHI-E was defined as a mean increase in Hb of ≥1.5 g/dL for 8 weeks in the absence of transfusions.
More patients receiving Reblozyl achieved a hematologic improvement through Week 48 vs placebo1
During Weeks 1-48:
- 58.8% of patients achieved mHI-E vs 17.1% for placebo1.
- 69.6% achieved a mean Hb increase of at least 1.5 g/dL for 8 weeks vs 5.0% for placebo1,c.
- 54.2% achieved a RBC transfusion reduction of 4 units/8 weeks vs 21.4% for placebo1,c.
Exploratory Endpoint: Modified hematologic improvement-erythroid (mHI-E)a,b,c • Weeks 1-481
More patients achieved mHI-E at Week 48 with Reblozyl vs placebo
aResponse criteria were developed by the IWG.
bThe proportion of patients meeting the HI-E criteria as per IWG 2006 criteria sustained over a consecutive 56-day period during the indicated treatment period.
cIn patients with a baseline transfusion burden of ≥4 units/8 weeks, mHI-E was defined as a reduction in RBC transfusions of at least 4 units/8 weeks. For patients with a baseline RBC burden of <4 units/8 weeks, mHI-E was defined as a mean increase in Hb of ≥1.5 g/dL for 8 weeks in the absence of transfusions.
Improve hemoglobin levels
Erythroid maturation for achieving hematologic improvement
More patients on Reblozyl achieved a hematologic improvement, according to the International Working Group (IWG) 2006 response criteria, during Weeks 1-24.1
Exploratory Endpoint: Modified hematologic
improvement-erythroid (mHI-E)a,b,c Weeks 1-241
More patients achieved mHI-E at Week 24 with Reblozyl vs placebo1
- 63.0% achieved a mean hemoglobin (Hb) increase of at least 1.5 g/dL for 8 weeks vs 5.0% for placebo1,c
- 48.6% achieved a RBC transfusion reduction of 4 units/8 weeks vs 14.3% for placebo1,c
aResponse criteria were developed by the IWG.
bThe proportion of patients meeting the HI-E criteria as per IWG 2006 criteria sustained over a consecutive 56-day period during the indicated treatment period.
cIn patients with a baseline transfusion burden of ≥4 units/8 weeks, mHI-E was defined as a reduction in RBC transfusions of at least 4 units/8 weeks. For patients with a baseline RBC burden of <4 units/8 weeks, mHI-E was defined as a mean increase in hemoglobin of ≥1.5 g/dL for 8 weeks in the absence of transfusions.
Exploratory endpoint: mHI-E improvement up to Week 48 with Reblozyl
Exploratory Endpoint: mHI-Ea,b,c Weeks 1-481
More patients achieved mHI-E at Week 48 with Reblozyl vs placebo1
- 69.6% achieved a mean Hb increase of at least 1.5 g/dL for 8 weeks vs 5.0% for placebo1,c.
- 54.2% achieved a RBC transfusion reduction of 4 units/8 weeks vs 21.4% for placebo1,c.
aResponse criteria were developed by the IWG.
bThe proportion of patients meeting the HI-E criteria as per IWG 2006 criteria sustained over a consecutive 56-day period during the indicated treatment period.
cIn patients with a baseline transfusion burden of ≥4 units/8 weeks, mHI-E was defined as a reduction in RBC transfusions of at least 4 units/8 weeks. For patients with a baseline RBC burden of <4 units/8 weeks, mHI-E was defined as a mean increase in hemoglobin of ≥1.5 g/dL for 8 weeks in the absence of transfusions.1
The efficacy and safety outcomes for Reblozyl were evaluated
in the pivotal phase 3 MEDALIST trial1-3
MEDALIST (ACE-536-MDS-001) was a global, randomized, double-blind, placebo-controlled Phase 3 trial involving adult patients with anemia requiring RBC transfusions (≥2 units/8 weeks) due to IPSS-R very low-, low-, or intermediate-risk MDS, who have RS (with either ≥15% ring sideroblasts or ≥5% ring sideroblasts if an SF3B1 mutation was present). Patients were required to have either received prior treatment with an ESA with inadequate response, to be ineligible for ESAs (determined to be unlikely to respond to ESA treatment with serum EPO >200 U/L), or intolerant to ESA treatment.1
Primary endpoint: RBC transfusion independence (RBC-TI) ≥8 weeks (Weeks 1-24)1
References: 1. Reblozyl® (luspatercept) Summary of Product Characteristics (SmPC). Celgene 2020. 2. Fenaux P, Haase D, Sanz GF, Santini V, Buske C; on behalf of the ESMO Guidelines Working Group. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(suppl 3):iii57-iii69. 3. Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382:140-151.
The efficacy and safety outcomes for Reblozyl were evaluated in the pivotal Phase 3 MEDALIST trial1,2
MEDALIST (ACE-536-MDS-001) was a global, randomized, double-blind, placebo-controlled Phase 3 trial involving adult patients with anemia requiring RBC transfusions (≥2 units/8 weeks) due to IPSS-R very low-, low-, or intermediate-risk MDS, who have RS (with either ≥15% ring sideroblasts or ≥5% ring sideroblasts if an SF3B1 mutation was present). Patients were required to have either received prior treatment with an ESA with inadequate response, to be ineligible for ESAs (determined to be unlikely to respond to ESA treatment with serum EPO >200 U/L), or intolerant to ESA treatment.1
Primary endpoint: RBC transfusion independence (RBC-TI) ≥8 weeks (Weeks 1-24)1
References:
1. Reblozyl® (luspatercept) Summary of Product Characteristics (SmPC). Celgene 2020.
2. Fenaux P, Platzbecker, GJ, Mufti G et al. Luspatercept patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382:149-151.
Rapid and sustained response
Response to Reblozyl treatment was rapid and sustained.1
- The median duration of the longest RBC-TI period among responders in the Reblozyl treatment arm was 30.6 weeks1
- With Reblozyl, hemoglobin began to increase within 7 days from treatment initiation in patients who received <4 units of RBC transfusions within 8 weeks prior to the study1
Reblozyl treatment response1,2
aFor patients with baseline RBC transfusion burden of <4 units within 8 weeks prior to the study.1
Rapid and sustained response
Response to Reblozyl treatment was rapid and sustained.1
Reblozyl treatment response1,2
aFor patients with baseline RBC transfusion burden of <4 units within 8 weeks prior to the study.1
- The median duration of the longest RBC-TI period among responders in the Reblozyl treatment arm was 30.6 weeks1
- With Reblozyl, hemoglobin began to increase within 7 days from treatment initiation in patients who received <4 units of RBC transfusions within 8 weeks prior to the study 1
The efficacy and safety outcomes for Reblozyl were evaluated
in the pivotal phase 3 MEDALIST trial1-3
MEDALIST (ACE-536-MDS-001) was a global, randomized, double-blind, placebo-controlled Phase 3 trial involving adult patients with anemia requiring RBC transfusions (≥2 units/8 weeks) due to IPSS-R very low-, low-, or intermediate-risk MDS, who have RS (with either ≥15% ring sideroblasts or ≥5% ring sideroblasts if an SF3B1 mutation was present). Patients were required to have either received prior treatment with an ESA with inadequate response, to be ineligible for ESAs (determined to be unlikely to respond to ESA treatment with serum EPO >200 U/L), or intolerant to ESA treatment.1
Primary endpoint: RBC transfusion independence (RBC-TI) ≥8 weeks (Weeks 1-24)1
References: 1. Reblozyl® (luspatercept) Summary of Product Characteristics (SmPC). Celgene 2020. 2. Fenaux P, Haase D, Sanz GF, Santini V, Buske C; on behalf of the ESMO Guidelines Working Group. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(suppl 3):iii57-iii69. 3. Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382:140-151.
The efficacy and safety outcomes for Reblozyl were evaluated in the pivotal Phase 3 MEDALIST trial1,2
MEDALIST (ACE-536-MDS-001) was a global, randomized, double-blind, placebo-controlled Phase 3 trial involving adult patients with anemia requiring RBC transfusions (≥2 units/8 weeks) due to IPSS-R very low-, low-, or intermediate-risk MDS, who have RS (with either ≥15% ring sideroblasts or ≥5% ring sideroblasts if an SF3B1 mutation was present). Patients were required to have either received prior treatment with an ESA with inadequate response, to be ineligible for ESAs (determined to be unlikely to respond to ESA treatment with serum EPO >200 U/L), or intolerant to ESA treatment.1
Primary endpoint: RBC transfusion independence (RBC-TI) ≥8 weeks (Weeks 1-24)1
References:
1. Reblozyl® (luspatercept) Summary of Product Characteristics (SmPC). Celgene 2020.
2. Fenaux P, Platzbecker, GJ, Mufti G et al. Luspatercept patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382:149-151.
Impact serum ferritin levels
Lower mean serum ferritin levels were observed from baseline with Reblozyl compared with placebo.1
- At Weeks 9-24, mean serum ferritin had increased 9.9 μg/L with Reblozyl vs an increase of 190 μg/L with placebo1
- The least square mean difference (SE) was –180.1 μg/L
Exploratory Endpoint: Impact on serum ferritin levels with Reblozyl1
Impact Serum Ferritin Levels
Lower mean serum ferritin levels were observed from baseline with Reblozyl compared with placebo.1
Exploratory Endpoint: Impact on serum ferritin levels with Reblozyl1
- At Weeks 9-24, mean serum ferritin had increased 9.9 μg/L with Reblozyl vs an increase of 190 μg/L with placebo1
- The least square mean difference (SE) was -180.1 μg/L
The efficacy and safety outcomes for Reblozyl were evaluated
in the pivotal phase 3 MEDALIST trial1-3
MEDALIST (ACE-536-MDS-001) was a global, randomized, double-blind, placebo-controlled Phase 3 trial involving adult patients with anemia requiring RBC transfusions (≥2 units/8 weeks) due to IPSS-R very low-, low-, or intermediate-risk MDS, who have RS (with either ≥15% ring sideroblasts or ≥5% ring sideroblasts if an SF3B1 mutation was present). Patients were required to have either received prior treatment with an ESA with inadequate response, to be ineligible for ESAs (determined to be unlikely to respond to ESA treatment with serum EPO >200 U/L), or intolerant to ESA treatment.1
Primary endpoint: RBC transfusion independence (RBC-TI) ≥8 weeks (Weeks 1-24)1
References: 1. Reblozyl® (luspatercept) Summary of Product Characteristics (SmPC). Celgene 2020. 2. Fenaux P, Haase D, Sanz GF, Santini V, Buske C; on behalf of the ESMO Guidelines Working Group. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(suppl 3):iii57-iii69. 3. Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382:140-151.
The efficacy and safety outcomes for Reblozyl were evaluated in the pivotal Phase 3 MEDALIST trial1,2
MEDALIST (ACE-536-MDS-001) was a global, randomized, double-blind, placebo-controlled Phase 3 trial involving adult patients with anemia requiring RBC transfusions (≥2 units/8 weeks) due to IPSS-R very low-, low-, or intermediate-risk MDS, who have RS (with either ≥15% ring sideroblasts or ≥5% ring sideroblasts if an SF3B1 mutation was present). Patients were required to have either received prior treatment with an ESA with inadequate response, to be ineligible for ESAs (determined to be unlikely to respond to ESA treatment with serum EPO >200 U/L), or intolerant to ESA treatment.1
Primary endpoint: RBC transfusion independence (RBC-TI) ≥8 weeks (Weeks 1-24)1
References:
1. Reblozyl® (luspatercept) Summary of Product Characteristics (SmPC). Celgene 2020.
2. Fenaux P, Platzbecker, GJ, Mufti G et al. Luspatercept patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382:149-151.
Various patient groups benefit
A treatment effect in favor of Reblozyl over placebo was observed in most subgroups analyzed using transfusion independence ≥12 weeks (during week 1 to week 24).1
Reblozyl demonstrated greater transfusion independence
≥12 weeks in most subgroups analyzed, including*1:
Patients with high baseline ENDOGENOUS EPO levels (200-500 U/L) (23.3% vs 0%, explorative analysis)
*Analyzed using transfusion independence ≥12 weeks (during Week 1 to Week 24).1
Various patient groups benefit
Reblozyl demonstrated efficacy across various patient groups1
A treatment effect in favor of Reblozyl over placebo was observed in most subgroups analyzed using transfusion independence ≥12 weeks (during week 1 to week 24).1
Reblozyl demonstrated greater transfusion independence ≥12 weeks in most subgroups analyzed, including*1:
Patients with high baseline ENDOGENOUS EPO levels (200-500 U/L) (23.3% vs 0%, explorative analysis)
*Analyzed using transfusion independence ≥12 weeks (during Week 1 to Week 24).1
The efficacy and safety outcomes for Reblozyl were evaluated
in the pivotal phase 3 MEDALIST trial1-3
MEDALIST (ACE-536-MDS-001) was a global, randomized, double-blind, placebo-controlled Phase 3 trial involving adult patients with anemia requiring RBC transfusions (≥2 units/8 weeks) due to IPSS-R very low-, low-, or intermediate-risk MDS, who have RS (with either ≥15% ring sideroblasts or ≥5% ring sideroblasts if an SF3B1 mutation was present). Patients were required to have either received prior treatment with an ESA with inadequate response, to be ineligible for ESAs (determined to be unlikely to respond to ESA treatment with serum EPO >200 U/L), or intolerant to ESA treatment.1
Primary endpoint: RBC transfusion independence (RBC-TI) ≥8 weeks (Weeks 1-24)1
References: 1. Reblozyl® (luspatercept) Summary of Product Characteristics (SmPC). Celgene 2020. 2. Fenaux P, Haase D, Sanz GF, Santini V, Buske C; on behalf of the ESMO Guidelines Working Group. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(suppl 3):iii57-iii69. 3. Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382:140-151.
The efficacy and safety outcomes for Reblozyl were evaluated in the pivotal Phase 3 MEDALIST trial1,2
MEDALIST (ACE-536-MDS-001) was a global, randomized, double-blind, placebo-controlled Phase 3 trial involving adult patients with anemia requiring RBC transfusions (≥2 units/8 weeks) due to IPSS-R very low-, low-, or intermediate-risk MDS, who have RS (with either ≥15% ring sideroblasts or ≥5% ring sideroblasts if an SF3B1 mutation was present). Patients were required to have either received prior treatment with an ESA with inadequate response, to be ineligible for ESAs (determined to be unlikely to respond to ESA treatment with serum EPO >200 U/L), or intolerant to ESA treatment.1
Primary endpoint: RBC transfusion independence (RBC-TI) ≥8 weeks (Weeks 1-24)1
References:
1. Reblozyl® (luspatercept) Summary of Product Characteristics (SmPC). Celgene 2020.
2. Fenaux P, Platzbecker, GJ, Mufti G et al. Luspatercept patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382:149-151.