The long-term benefit of luspatercept: analysis from the phase III MEDALIST trial

Luspatercept, a first-in-class erythroid maturation agent, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of anemia in transfusion-dependent patients with lower-risk myelodysplastic syndromes with ring sideroblasts who are refractory/intolerant to erythropoiesis-stimulating agents.¹

Approval was based on results from the phase III MEDALIST trial (NCT02631070).¹ Recently, Platzbecker et al.¹ published a long-term analysis of MEDALIST in Leukemia, we are pleased to summarize the key points below.

Study design and patient population

Study design, patient characteristics, and results from the phase III MEDALIST trial have been previously reported by the MDS Hub. The long-term follow-up data cutoff was January 15, 2021.

Median follow-up time was 39.9 and 38.4 months and median duration of treatment of 11.70 and 5.52 months in the luspatercept and placebo arms, respectively.

Key findings

At the long-term follow-up data cutoff, red blood cell transfusion independence and an increase in hemoglobin level were experienced by a higher proportion of patients in the luspatercept arm vs placebo (Figure 1).

Figure 1. RBC-TI and increase in Hb in the MEDALIST trial* 

Hb, hemoglobin; RBC-TI, red blood cell transfusion independence.
*Data from Platzbecker, et al.¹

The rate of progression to higher-risk MDS (5.9% vs 3.9%) and acute myeloid leukemia (5.9% vs 3.9%) was low in both the luspatercept and placebo arms, respectively.

Overall survival in all patients and by response is shown in Figure 2.

Figure 2. Overall survival in A all patients, B RBC-TI ≥8 weeks response during Weeks 1–24, C RBC-TI ≥16 weeks response during Weeks 1–24, and D Hb increase ≥1.5 g/dl response during Weeks 1–24*

Hb, hemoglobin; RBC-TI, red blood cell transfusion-independence.
*Adapted from Platzbecker, et al.¹

Response to luspatercept during Weeks 1–24 was associated with longer overall survival in the luspatercept arm (Figure 3).

Figure 3. Median duration of OS*

CI, confidence interval; Hb, hemoglobin; HR, hazard ratio; NR, not reached; OS, overall survival; RBC-TI, red blood cell transfusion-independence.
*Adapted from Platzbecker, et al.¹

Key learnings

This analysis highlighted the long-term benefit of luspatercept for the treatment of anemia in this patient population, with continued benefits shown for over 2 years. Response to luspatercept was associated with longer overall survival when compared to non-responders.