Contributions
Abstract: EP915
Type: E-Poster Presentation
Session title: Myelodysplastic syndromes - Clinical
Background
MEDALIST (NCT02631070) is an ongoing, randomized, placebo-controlled phase 3 trial evaluating the efficacy and safety of luspatercept, the first and only erythroid maturation agent, in patients with anemia due to lower-risk myelodysplastic syndromes (LR-MDS) with ring sideroblasts. A greater proportion of patients receiving luspatercept than placebo achieved the primary endpoint of red blood cell transfusion independence (RBC-TI) for ≥8 weeks during Weeks 1–24 (Fenaux P, et al. N Engl J Med 2020;382:140-151). However, for patients not achieving the primary endpoint during the first 24 weeks, the value of continuing luspatercept treatment is not yet well understood.
Aims
To evaluate the clinical benefit of continuing luspatercept treatment beyond 24 weeks in patients not achieving the RBC-TI primary endpoint during the first 24 weeks of the MEDALIST study.
Methods
Eligible patients were aged ≥18 years; were refractory, intolerant, or unlikely to respond to erythropoiesis-stimulating agents; and required regular RBC transfusions (≥2 units/8 weeks) in the 16 weeks prior to randomization. Overall, 229 patients were randomized 2:1 to receive either luspatercept (n=153) or placebo (n=76) every 3 weeks through the clinical assessment visit at Week 25, defined as 24 calendar weeks after the first dose, regardless of dose delays. Patients who did not achieve RBC-TI for ≥8 weeks on luspatercept by Week 25 but continued treatment were included in this analysis; the data cutoff was July 1, 2019. For this analysis, transfusion burden, serum ferritin (SF) levels, and hematologic improvement-erythroid (HI-E) response were assessed every 24 weeks. HI-E response was defined as a reduction in RBC transfusions of ≥4 units/8 weeks (for patients with baseline RBC transfusion burden of ≥4 units/8 weeks) or as an increase in hemoglobin level of ≥1.5 g/dL over 8 weeks (for patients with baseline RBC transfusion burden of <4 units/8 weeks).
Results
Of the patients receiving luspatercept, 68 did not meet the primary endpoint during the first 24 weeks and continued treatment. During Weeks 25–48, 16.2% (n=11/68) of these patients achieved RBC‑TI for ≥8 weeks for the first time, and a mean change from baseline of −1.3 RBC units transfused was achieved in 36 pts. 44.1% (n=30/68) of patients who did not meet the primary endpoint achieved any degree of reduction in SF levels from baseline during Weeks 25–48, while 17.9% (n=7/39) shifted from a SF level ≥1,000 µg/L at baseline to <1,000 µg/L. During Weeks 1–48, 60.3% (n=41/68) of patients who did not meet the primary endpoint achieved ≥50% reduction in RBC transfusion burden for ≥8 weeks from baseline and 47.1% (n=32/68) achieved HI-E response. Over the entire treatment period up to the data cutoff, 60.3% (n=41/68) achieved ≥50% reduction in transfusion burden for ≥8 weeks from baseline, 22.1% (n=15/68) achieved RBC-TI for ≥8 weeks, and 48.5% (n=33/68) achieved HI-E response.
Conclusion
A considerable proportion of patients with LR-MDS in the MEDALIST study who did not achieve the primary endpoint, but continued to receive luspatercept beyond 24 weeks of treatment, experienced a broad range of clinical improvements, including reduced transfusion burden, reduced SF levels, and even TI.
Keyword(s): Clinical trial, MDS, Phase III, Transfusion
Abstract: EP915
Type: E-Poster Presentation
Session title: Myelodysplastic syndromes - Clinical
Background
MEDALIST (NCT02631070) is an ongoing, randomized, placebo-controlled phase 3 trial evaluating the efficacy and safety of luspatercept, the first and only erythroid maturation agent, in patients with anemia due to lower-risk myelodysplastic syndromes (LR-MDS) with ring sideroblasts. A greater proportion of patients receiving luspatercept than placebo achieved the primary endpoint of red blood cell transfusion independence (RBC-TI) for ≥8 weeks during Weeks 1–24 (Fenaux P, et al. N Engl J Med 2020;382:140-151). However, for patients not achieving the primary endpoint during the first 24 weeks, the value of continuing luspatercept treatment is not yet well understood.
Aims
To evaluate the clinical benefit of continuing luspatercept treatment beyond 24 weeks in patients not achieving the RBC-TI primary endpoint during the first 24 weeks of the MEDALIST study.
Methods
Eligible patients were aged ≥18 years; were refractory, intolerant, or unlikely to respond to erythropoiesis-stimulating agents; and required regular RBC transfusions (≥2 units/8 weeks) in the 16 weeks prior to randomization. Overall, 229 patients were randomized 2:1 to receive either luspatercept (n=153) or placebo (n=76) every 3 weeks through the clinical assessment visit at Week 25, defined as 24 calendar weeks after the first dose, regardless of dose delays. Patients who did not achieve RBC-TI for ≥8 weeks on luspatercept by Week 25 but continued treatment were included in this analysis; the data cutoff was July 1, 2019. For this analysis, transfusion burden, serum ferritin (SF) levels, and hematologic improvement-erythroid (HI-E) response were assessed every 24 weeks. HI-E response was defined as a reduction in RBC transfusions of ≥4 units/8 weeks (for patients with baseline RBC transfusion burden of ≥4 units/8 weeks) or as an increase in hemoglobin level of ≥1.5 g/dL over 8 weeks (for patients with baseline RBC transfusion burden of <4 units/8 weeks).
Results
Of the patients receiving luspatercept, 68 did not meet the primary endpoint during the first 24 weeks and continued treatment. During Weeks 25–48, 16.2% (n=11/68) of these patients achieved RBC‑TI for ≥8 weeks for the first time, and a mean change from baseline of −1.3 RBC units transfused was achieved in 36 pts. 44.1% (n=30/68) of patients who did not meet the primary endpoint achieved any degree of reduction in SF levels from baseline during Weeks 25–48, while 17.9% (n=7/39) shifted from a SF level ≥1,000 µg/L at baseline to <1,000 µg/L. During Weeks 1–48, 60.3% (n=41/68) of patients who did not meet the primary endpoint achieved ≥50% reduction in RBC transfusion burden for ≥8 weeks from baseline and 47.1% (n=32/68) achieved HI-E response. Over the entire treatment period up to the data cutoff, 60.3% (n=41/68) achieved ≥50% reduction in transfusion burden for ≥8 weeks from baseline, 22.1% (n=15/68) achieved RBC-TI for ≥8 weeks, and 48.5% (n=33/68) achieved HI-E response.
Conclusion
A considerable proportion of patients with LR-MDS in the MEDALIST study who did not achieve the primary endpoint, but continued to receive luspatercept beyond 24 weeks of treatment, experienced a broad range of clinical improvements, including reduced transfusion burden, reduced SF levels, and even TI.
Keyword(s): Clinical trial, MDS, Phase III, Transfusion