Garcia-Manero Guillermo, Santini Valeria, Zeidan Amer M, Komrokji Rami S, Pozharskaya Veronika, Rose Shelonitda, Keeperman Karen, Lai Yinzhi, Kalsekar Sameer, Aggarwal Barkha, Miteva Dimana, Valcárcel David, Fenaux Pierre, Shortt Jake, Della Porta Matteo Giovanni, Platzbecker Uwe
MD Anderson Cancer Center, Houston, TX, USA.
MDS Unit, DMSC, University of Florence, AOUC, Florence, Italy.
Adv Ther. 2025 May 16. doi: 10.1007/s12325-025-03208-5.
The efficacy of erythropoiesis-stimulating agents (ESAs) for transfusion-dependent (TD) anemia in lower-risk myelodysplastic syndromes (LR-MDS) is limited. Luspatercept achieved significantly greater rates of red blood cell (RBC) transfusion independence (TI) versus epoetin alfa (an ESA) in the phase 3 COMMANDS trial. This analysis assessed long-term RBC-TI, cumulative response, and safety with luspatercept in COMMANDS.
Eligible patients aged ≥ 18 years, with ESA-naive, RBC TD LR-MDS were randomized 1:1 to receive luspatercept (1.0 mg/kg, titration to 1.75 mg/kg permitted) or epoetin alfa (450 IU/kg, titration to 1050 IU/kg). Disease assessment was carried out at week 24 (day 169) and every 24 weeks thereafter. Treatment continued until disease progression, lack of clinical benefit, unacceptable toxicity, or consent withdrawal.
At data cutoff (September 22, 2023; median follow-up: luspatercept 21.4 months, epoetin alfa 20.3 months), a greater proportion of patients treated with luspatercept (n = 182) versus epoetin alfa (n = 181) achieved a longest single RBC-TI period ≥ 1 year (44.5% vs. 27.6%; P = 0.0003) and ≥ 1.5 years (30.2% vs. 13.8%; P < 0.0001). Higher rates of RBC-TI ≥ 1.5 years with luspatercept over epoetin alfa were consistent across all prespecified subgroups, including patients with ring sideroblast-negative status and low baseline serum erythropoietin. Longer cumulative RBC-TI response [sum of all durations of RBC-TI for ≥ 12 weeks; week 1 to end of treatment (95% CI)] was observed with luspatercept [154.7 weeks (118.4-NR)] versus epoetin alfa [91.1 weeks (73.1-123.9)]. Rates of treatment-emergent adverse events, including asthenia and hypertension, generally decreased over time in both arms. Progression rates to high-risk MDS and acute myeloid leukemia were similarly low (< 5%) in both treatment arms.
These data demonstrated sustained, durable clinical benefit across subgroups and support luspatercept as the treatment of choice for anemia in patients with LR-MDS who are TD and ESA-naive.
NCT03682536.
促红细胞生成素（ESA）对低危骨髓增生异常综合征（LR-MDS）中依赖输血的（TD）贫血的疗效有限。在3期COMMANDS试验中，与促红细胞生成素α（一种ESA）相比，罗特西普实现红细胞（RBC）输血独立（TI）的比例显著更高。该分析评估了COMMANDS试验中罗特西普的长期RBC-TI、累积反应和安全性。
年龄≥18岁、未使用过ESA、RBC TD的LR-MDS合格患者按1:1随机分组，接受罗特西普（1.0mg/kg，允许滴定至1.75mg/kg）或促红细胞生成素α（450IU/kg，滴定至1050IU/kg）。在第24周（第169天）及之后每24周进行疾病评估。治疗持续至疾病进展、缺乏临床获益、出现不可接受的毒性或患者撤回同意书。
在数据截止时（2023年9月22日；中位随访时间：罗特西普组21.4个月，促红细胞生成素α组20.3个月），与促红细胞生成素α组（n = 181）相比，接受罗特西普治疗的患者（n = 182）中更长单次RBC-TI期≥1年（44.5%对27.6%；P = 0.0003）和≥1.5年（30.2%对13.8%；P < 0.0001）的比例更高。在所有预先指定的亚组中，包括环形铁粒幼细胞阴性状态和低基线血清促红细胞生成素的患者，罗特西普组RBC-TI≥1.5年的发生率均高于促红细胞生成素α组。与促红细胞生成素α组[91.1周（73.1 - 123.9）]相比，罗特西普组观察到更长的累积RBC-TI反应[RBC-TI持续≥12周的所有时长之和；第1周治疗结束（95%CI）][154.7周（118.4 - NR）]。包括乏力和高血压在内的治疗中出现的不良事件发生率在两组中一般随时间下降。两个治疗组进展为高危MDS和急性髓系白血病的发生率同样较低（<5%）。
这些数据表明罗特西普在各亚组中均具有持续、持久的临床获益，并支持罗特西普作为TD且未使用过ESA的LR-MDS患者贫血的首选治疗药物。
NCT03682536
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