Included studies’ characteristics
| Author (year) . | Study design . | Center . | Patients, n . | Age, y . | Population characteristics . | Previous Tx/current Tx . | Outcome of interest . | Main result . | Quality assessment . |
|---|---|---|---|---|---|---|---|---|---|
| Della Porta et al13 (2024) | RCT (phase 3) Full article | Multi | 363 (Lusp, 182; ESA, 181) | Med: 74 | ESA naïve and RS+: 73% IPSS-R: LR | N/A | Primary outcome: 12-week TI Secondary outcome: 8-week HI-E and TI at 8, 24, and 48 weeks, and safety profile | Lusp 12-week TI: 60% ESA 12-week TI: 35% | Excellent |
| Fenaux et al16 (2020) | RCT (phase 3) Full article | Multi | 153 (Lusp, 76; placebo, 76) | Med: 71 | IPSS-R: VL, L, and I risk ESA refractory and RS+ | ESA and ICA/N/A | Primary outcome: 8-week TI Secondary outcome: 12-week TI, HI-E, and safety profile | Lusp 8-week TI: 38% Placebo 8-week TI: 13% | Excellent |
| Patel et al5 (2024) | Retro Cohort Abstract | Multi | 240 Lusp | Mean: 75.4 | ESA exposed (relapsed/refractory) | ESA and other (–)/N/A | Primary outcome: 8-week TI Secondary outcome: 12-, 16-, and 24-week TI | 8-week TI: 64.2% | Good |
| Patel et al41 (2023) | Retro Cohort Abstract | Multi | 279 Lusp | Med: 76 | IPSS-R: VL, L, and I risk ESA (naïve, refractory, or relapsed) | Lusp: 1L (30), 2L (202), and 3L (59)/1L (7 ESA), 2L (39 ESA and 5 HMA/IMID), and 3L (13 ESA, 10 HMA, and 3 IMID) | Primary outcome: 8-week TI Secondary outcome: 12-, 16-, and 24-week TI | 1L: 77% at 8-week TI 2L: 66% at 8-week TI 3L: 58% at 8-week | Good |
| Platzbecker et al42 (2022) | CT (phase 2) Full article | Multi | 74 | Med: 72.5 | IPSS-R: VL, L, I risk RS+/– | ESA 43.2%, ICA 31.9%, and IMID 9.5% | Primary outcome: 8-week TI Secondary outcome: 8-week HI-E and safety profile | 8-week TI: 43.8% | Excellent |
| Al Ali et al28 (2023) | Retro Cohort Abstract | Single (MCC) | 28 | Med: 72 | IPSS-R: VL, L, and I risk RS+/– ESA + Lusp | Primary failure Lusp, n = 18; secondary failure Lusp, n = 7; and Lusp + ESA failure, n = 3/Lusp + ESA, n = 28 | Primary outcome: HI | HI was 36% | Fair |
| Batra et al30 (2023) | Retro Cohort Full article | Multi | 592 | Mean: 69.6 | IPSS-R: VL, L, and I risk RS+/– | N/A | Primary outcome: AEs | Fatigue is the most common | Good |
| Ades et al27 (2024) | CT (phase 2) Abstract | N/A | 24 | Med: 77.7 | IPSS-R: VL, L, and I risk RS– | ESA, 100%/Lusp + ESA | Primary outcome: 8-week TI | 8-week TI: 29% | Good |
| Andritsos et al29 (2025) | Retro Cohort Full article | Multi | 871 | Mean: 74.7 | IPSS-R: VL, L, and I risk RS+/– | ESA, 84.7%/Lusp only and Lusp + ESA | Primary outcome: 8-week TI Secondary outcome: 12- and 24-week TI and HI | 8-week TI for TD (Lusp only and Lusp + ESA): 64.2% | Excellent |
| Bouchla et al31 (2024) | Retro Cohort Full article | Multi | 98 | Mean: 75 | IPSS-R: VL, L, and I risk RS+/– | ESA, 95/98 | Primary outcome: 8-week TI Secondary outcome: 12-week TI and AEs | 8-week TI (HTB, 25%; ITB, 57%; LTB, 69%) | Good |
| Chang et al12 (2025) | CT (phase 2) Full article | Multi | 37 | Med: 65 | IPSS-R: VL, L, and I risk RS+ | ESA, 57% | Primary outcome: 8-week TI Secondary outcome: 12-week TI, HI, and AEs | 8-week TI: 60% | Good |
| Comont et al32 (2023) | Prosp Cohort Abstract | Multi | 108 | Med: 70 | IPSS-R: VL, L, and I risk RS+/– | ESA, 100%; others, 44% | Primary outcome: 8-week HI-E | 8-week HI-E: 39% | Excellent |
| Consagra et al33 (2025) | CT Full article | Single (MCC) | 331 | Med: 75 | IPSS-R: VL, L, and I risk RS+/– | ESA, 95.8%; HMA, 15.7%; IMID, 11.5% | Primary outcome: 8-week TI Secondary outcome: increase in Hb 1.5 g/dL | 8-week TI: 16.6% | Excellent |
| Götze et al34 (2024) | RCT (phase 3) Abstract | Multi | 41 | Med: 72 | IPSS-R: VL, L, and I risk RS+ Max Lusp dose | N/A | Primary outcome: 8-week TI Secondary outcome: AEs | 8-week TI: 45.5% | Excellent |
| Heyrman et al35 (2024) | Retro Cohort Full article | Multi | 77 | Med: 79 | IPSS-R: VL, L, and I risk RS+/– | ESA, 70.1% | Primary outcome: 8-week TI | 8-week TI: 35.4% | Good |
| Jonasova et al36 (2024) | Retro Cohort Full article | Multi | 56 | Med: 74 | IPSS-R: VL, L, and I risk RS+/– | ESA, 83.3% | Primary outcome: 8-week TI Secondary outcome: 12- and 24-week HI-E | 8-week TI: 62.7% | Poor |
| Komrokji et al37 (2022) | Retro Cohort Abstract | Single (MCC) | 114 | Med: 70 | IPSS-R: VL, L, and I risk RS+/– | ESA, 89% | Primary outcome: HI Secondary outcome: TI | HI: 39.5% | Excellent |
| Lanino et al38 (2023) | Retro Cohort Full article | Single (Rozzano) | 215 | Med: 74 | IPSS-R: VL, L, and I risk RS+/– | N/A | Primary outcome: 8-week TI Secondary outcome: 12-week TI | 8-week TI (follow-up 24 week): 30.3% | Excellent |
| Leonard et al39 (2024) | Retro Cohort Abstract | Multi | 62 | Med: 78 | IPSS-R: VL, L, and I risk RS+/– | N/A | Primary outcome: HI | HI, 48% | Good |
| Mukherjee et al43 (2024) | Retro Cohort Full article | Multi | 253 | Med, 73.3 | IPSS-R: VL, L, and I risk | ESA, 87% | Primary outcome: TI at 8 weeks Secondary outcome: HI | 8-week TI: 79.4% (LTB, 89.9%; HTB, 58.3%) | Excellent |
| Author (year) . | Study design . | Center . | Patients, n . | Age, y . | Population characteristics . | Previous Tx/current Tx . | Outcome of interest . | Main result . | Quality assessment . |
|---|---|---|---|---|---|---|---|---|---|
| Della Porta et al13 (2024) | RCT (phase 3) Full article | Multi | 363 (Lusp, 182; ESA, 181) | Med: 74 | ESA naïve and RS+: 73% IPSS-R: LR | N/A | Primary outcome: 12-week TI Secondary outcome: 8-week HI-E and TI at 8, 24, and 48 weeks, and safety profile | Lusp 12-week TI: 60% ESA 12-week TI: 35% | Excellent |
| Fenaux et al16 (2020) | RCT (phase 3) Full article | Multi | 153 (Lusp, 76; placebo, 76) | Med: 71 | IPSS-R: VL, L, and I risk ESA refractory and RS+ | ESA and ICA/N/A | Primary outcome: 8-week TI Secondary outcome: 12-week TI, HI-E, and safety profile | Lusp 8-week TI: 38% Placebo 8-week TI: 13% | Excellent |
| Patel et al5 (2024) | Retro Cohort Abstract | Multi | 240 Lusp | Mean: 75.4 | ESA exposed (relapsed/refractory) | ESA and other (–)/N/A | Primary outcome: 8-week TI Secondary outcome: 12-, 16-, and 24-week TI | 8-week TI: 64.2% | Good |
| Patel et al41 (2023) | Retro Cohort Abstract | Multi | 279 Lusp | Med: 76 | IPSS-R: VL, L, and I risk ESA (naïve, refractory, or relapsed) | Lusp: 1L (30), 2L (202), and 3L (59)/1L (7 ESA), 2L (39 ESA and 5 HMA/IMID), and 3L (13 ESA, 10 HMA, and 3 IMID) | Primary outcome: 8-week TI Secondary outcome: 12-, 16-, and 24-week TI | 1L: 77% at 8-week TI 2L: 66% at 8-week TI 3L: 58% at 8-week | Good |
| Platzbecker et al42 (2022) | CT (phase 2) Full article | Multi | 74 | Med: 72.5 | IPSS-R: VL, L, I risk RS+/– | ESA 43.2%, ICA 31.9%, and IMID 9.5% | Primary outcome: 8-week TI Secondary outcome: 8-week HI-E and safety profile | 8-week TI: 43.8% | Excellent |
| Al Ali et al28 (2023) | Retro Cohort Abstract | Single (MCC) | 28 | Med: 72 | IPSS-R: VL, L, and I risk RS+/– ESA + Lusp | Primary failure Lusp, n = 18; secondary failure Lusp, n = 7; and Lusp + ESA failure, n = 3/Lusp + ESA, n = 28 | Primary outcome: HI | HI was 36% | Fair |
| Batra et al30 (2023) | Retro Cohort Full article | Multi | 592 | Mean: 69.6 | IPSS-R: VL, L, and I risk RS+/– | N/A | Primary outcome: AEs | Fatigue is the most common | Good |
| Ades et al27 (2024) | CT (phase 2) Abstract | N/A | 24 | Med: 77.7 | IPSS-R: VL, L, and I risk RS– | ESA, 100%/Lusp + ESA | Primary outcome: 8-week TI | 8-week TI: 29% | Good |
| Andritsos et al29 (2025) | Retro Cohort Full article | Multi | 871 | Mean: 74.7 | IPSS-R: VL, L, and I risk RS+/– | ESA, 84.7%/Lusp only and Lusp + ESA | Primary outcome: 8-week TI Secondary outcome: 12- and 24-week TI and HI | 8-week TI for TD (Lusp only and Lusp + ESA): 64.2% | Excellent |
| Bouchla et al31 (2024) | Retro Cohort Full article | Multi | 98 | Mean: 75 | IPSS-R: VL, L, and I risk RS+/– | ESA, 95/98 | Primary outcome: 8-week TI Secondary outcome: 12-week TI and AEs | 8-week TI (HTB, 25%; ITB, 57%; LTB, 69%) | Good |
| Chang et al12 (2025) | CT (phase 2) Full article | Multi | 37 | Med: 65 | IPSS-R: VL, L, and I risk RS+ | ESA, 57% | Primary outcome: 8-week TI Secondary outcome: 12-week TI, HI, and AEs | 8-week TI: 60% | Good |
| Comont et al32 (2023) | Prosp Cohort Abstract | Multi | 108 | Med: 70 | IPSS-R: VL, L, and I risk RS+/– | ESA, 100%; others, 44% | Primary outcome: 8-week HI-E | 8-week HI-E: 39% | Excellent |
| Consagra et al33 (2025) | CT Full article | Single (MCC) | 331 | Med: 75 | IPSS-R: VL, L, and I risk RS+/– | ESA, 95.8%; HMA, 15.7%; IMID, 11.5% | Primary outcome: 8-week TI Secondary outcome: increase in Hb 1.5 g/dL | 8-week TI: 16.6% | Excellent |
| Götze et al34 (2024) | RCT (phase 3) Abstract | Multi | 41 | Med: 72 | IPSS-R: VL, L, and I risk RS+ Max Lusp dose | N/A | Primary outcome: 8-week TI Secondary outcome: AEs | 8-week TI: 45.5% | Excellent |
| Heyrman et al35 (2024) | Retro Cohort Full article | Multi | 77 | Med: 79 | IPSS-R: VL, L, and I risk RS+/– | ESA, 70.1% | Primary outcome: 8-week TI | 8-week TI: 35.4% | Good |
| Jonasova et al36 (2024) | Retro Cohort Full article | Multi | 56 | Med: 74 | IPSS-R: VL, L, and I risk RS+/– | ESA, 83.3% | Primary outcome: 8-week TI Secondary outcome: 12- and 24-week HI-E | 8-week TI: 62.7% | Poor |
| Komrokji et al37 (2022) | Retro Cohort Abstract | Single (MCC) | 114 | Med: 70 | IPSS-R: VL, L, and I risk RS+/– | ESA, 89% | Primary outcome: HI Secondary outcome: TI | HI: 39.5% | Excellent |
| Lanino et al38 (2023) | Retro Cohort Full article | Single (Rozzano) | 215 | Med: 74 | IPSS-R: VL, L, and I risk RS+/– | N/A | Primary outcome: 8-week TI Secondary outcome: 12-week TI | 8-week TI (follow-up 24 week): 30.3% | Excellent |
| Leonard et al39 (2024) | Retro Cohort Abstract | Multi | 62 | Med: 78 | IPSS-R: VL, L, and I risk RS+/– | N/A | Primary outcome: HI | HI, 48% | Good |
| Mukherjee et al43 (2024) | Retro Cohort Full article | Multi | 253 | Med, 73.3 | IPSS-R: VL, L, and I risk | ESA, 87% | Primary outcome: TI at 8 weeks Secondary outcome: HI | 8-week TI: 79.4% (LTB, 89.9%; HTB, 58.3%) | Excellent |
1L, first line of therapy; CT, clinical trial; HMA, hypomethylating agent; HTB, high transfusion burden; ICA, immunosuppressive chemotherapy agent; I, intermediate; IMID, immunomodulatory drug; IPSS-R, revised IPSS; L, low; Lusp, luspatercept; Max, maximum; MCC, Moffitt Cancer Center; Med, median; N/A, not applicable; Prosp, prospective; RCT, randomized controlled trial; Retro, retrospective; Tx, treatment; VL, very low.