| Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access |
| Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc |
| Journal website https://jh.elmerpub.com |
Review
Volume 15, Number 2, April 2026, pages 51-70
Luspatercept: From Bench to Bedside and Beyond in the Management of Ineffective Erythropoiesis
Tables
| Trial name | Study type | Year of publication | Disease focus | Primary endpoint | Results, % of Luspatercept responders |
|---|---|---|---|---|---|
| Sources: BEYOND trial [34], BELIEVE trial [33], PACE-MDS trial [28], MEDALIST trial [3], COMMANDS trial [29–31], MEDALIST MDS/MPN RS-T sub study [32] and ACE -536 MF-001 trial [27]. | |||||
| BEYOND [34] | Phase 2, randomized, double-blind, placebo | 2022 | Non–transfusion-dependent β-thalassemia | Hb ↑ ≥ 1 g/dL from baseline for ≥ 2 weeks during weeks 13–24 | 77.1% vs. 0% in placebo arm; P < 0.0001 |
| BELIEVE [33] | Phase 3, randomized, double-blind, placebo | 2020 | Transfusion-dependent β-thalassemia | ≥ 33% reduction in transfusion burden during weeks 13–24 and reduction in ≥ 2 RBC transfusion units | 21.4% vs. 4.5% in placebo arm; P < 0.001 |
| PACE-MDS [28] | Phase 2, open-label | 2019 | Lower-risk MDS (RS and non-RS) | Hematologic improvement–erythroid (HI-E) per IWG 2006 criteria | Non-RS: 36.4%; RS: 67.7%; Overall: 53.7% |
| MEDALIST [3] | Phase 3, randomized, double-blind, placebo | 2020 | Lower-risk MDS with ring sideroblasts | ≥ 8 weeks of RBC transfusion independence (RBC-TI) during first 24 weeks | 38% vs. 13% in placebo arm; P < 0.001 |
| COMMANDS [29–31] | Phase 3, randomized, open-label | 2023 | ESA-naive, lower-risk MDS | ≥ 12 weeks RBC-TI + mean Hb ↑ ≥ 1.5 g/dL in weeks 1–24 | 58.5% (Luspatercept) vs. 31.2% (epoetin alfa); P < 0.0001 |
| MEDALIST MDS/MPN-RS-T Substudy [32] | Retrospective post-hoc analysis | 2020 | MDS/MPN-RS-T (retrospective) | ≥ 8 weeks RBC-TI during weeks 1–24 | 64.3% vs. 22.2% in placebo arm; P = 0.028 |
| ACE-536-MF-001 [27] | Phase 2, open-label | 2024 | Myelofibrosis (MF) | NTD: Hb ↑ ≥ 1.5 g/dL from baseline for 12 weeks; TD: ≥ 12 weeks RBC-TI | NTD: cohort 1: 14%, cohort 3A: 14% TD: cohort 2: 10%, cohort 3B: 26% |
| Safety outcome | BELIEVE (β-thalassemia) [33] | MEDALIST (MDS with RS) [3] | COMMANDS (LR-MDS, ESA-naive) [29–31] |
|---|---|---|---|
| Sources: BELIEVE trial [33], MEDALIST trial [3], COMMANDS trial [29–31]. | |||
| Most common adverse events (≥ 10%) | Fatigue (27%), headache (26%), bone pain (19%), arthralgia (19%), dizziness (15%), hypertension (10%) | Fatigue (27%), diarrhea (22%), asthenia (20%), nausea (20%), dizziness (14%) | Fatigue (19%), diarrhea (15%), headache (13%), nausea (13%), cough (11%) |
| Grade ≥ 3 adverse events | ∼19% of patients | ∼42% of patients | ∼26% of patients |
| Thromboembolic events | ∼4% overall (↑ risk in splenectomized) | Rare (< 1%) | ∼3% (including deep vein thrombosis and pulmonary embolism) |
| Hypertension | 10% (grade ≥ 3 in ∼1%) | 13% (grade ≥ 3 in 3%) | 7% (grade ≥ 3 in 1%) |
| Discontinuation due to AEs | ∼5% | ∼9% | ∼4% |
| Deaths related to treatment | None reported | One possibly treatment-related (cardiac) | None considered related to treatment |
| Hypersensitivity reactions | Rare (non-serious rash) | Rare | Rare |