Table 1.
Key Favorable and Unfavorable Results of Luspatercept for Patients With Myelodysplastic Syndromes and Beta-thalassemia (MEDALIST and BELIEVE Studies)
| Effect | Unit | Luspatercept | Placebo | Uncertainties/Strength of Evidence |
|---|---|---|---|---|
| Myelodysplastic syndromes | ||||
| Favorable effects | N = 153 | N = 76 | Cutoff date May 8, 2018 | |
| RBC-TI ≥ 8 wks (weeks 1–24) | Rate 95% CI | 37.91% 30.20%–46.10% | 13.16% 6.49%–22.87% | P < 0.0001 (primary endpoint) |
| RBC-TI ≥ 12 wks (weeks 1–48) | Rate 95% CI | 33.33% 25.93%–41.40% | 11.84% 5.56%–21.29% | Key secondary endpoint |
| RBC-TI ≥ 12 wks (weeks 1–24) | Rate 95% CI | 28.10% 21.14%–35.93% | 7.89% 2.95%–16.40% | Key secondary endpoint |
| Unfavorable effects | N = 269 | N = 76 | Cutoff date July 2019 | |
| Death on study | Patients (%) | 16 (5.9%) | 4 (5.3%) | MEDALIST study and uncontrolled phase 2 studies |
| Death off study | Patients (%) | 23 (8.6%) | 14 (18.4%) | MEDALIST study and uncontrolled phase 2 studies |
| Malignancies | Patients (%) | 25 (9.3%) | 1 (1.3%) | See above; driven by transformation to AML in patients with high-risk IPSS-R (phase 2 studies) |
| Kidney injury | Patients (%) | 27 (10.0%) | 5 (6.6%) | See above |
| Beta-thalassemia | ||||
| Favorable effects | N = 224 | N = 112 | Cutoff date May 11, 2018 | |
| RBC transfusion reduction ≥33% (weeks 13–24) | Rate 95% CI | 21.4% 16.2%–27.4% | 4.5% | P < 0.0001 (primary endpoint) |
| RBC transfusion reduction ≥33% (weeks 37–48) | Rate 95% CI | 19.6% 14.7%–25.5% | 3.6% | Key secondary endpoints (hierarchically tested) |
| RBC transfusion reduction ≥50% (weeks 13–24) | Rate 95% CI | 7.6% 4.5%–11.9% | 1.8% | Key secondary endpoints (hierarchically tested) |
| RBC transfusion reduction ≥50% (weeks 37–48) | Rate 95% CI | 10.3% 6.6%–15.0% | 0.9% | Key secondary endpoints (hierarchically tested) |
| Mean change in RBC transfusion (weeks 13–24) | RBC units | −0.67 | +0.66 | Key secondary endpoints (hierarchically tested) |
| Unfavorable effects | N = 379 | N = 109 | Cutoff date July 2019 | |
| Death on study | Patients (%) | 3 (0.8%) | 1 (0.9%) | MEDALIST study and uncontrolled phase 2 studies |
| Death off study | Patients (%) | 3 (0.8%) | 0 (0%) | MEDALIST study and uncontrolled phase 2 studies |
| Malignancies | Patients (%) | 4 (1.1%) | 0 (0%) | See above; includes unlikely AML case, splenectomy and increased HCG |
| Kidney injury | Patients (%) | 21 (5.5%) | 3 (2.8%) | See above |
AML = acute myeloid leukemia; CI = confidence interval; TI = transfusion independence; RBC = red blood cell.