Recombinant human erythropoietin plus all-trans retinoic acid and testosterone undecanoate for the treatment of anemia in patients with lower-risk myelodysplastic syndromes: a multicenter, single-arm, prospective trial

Erythropoiesis-stimulating agents (ESAs) achieve hematological improvement-erythroid (HIE) in only 30% of ESA-naïve lower risk myelodysplastic syndrome (LR-MDS) patients with anemia, highlighting the need for developing novel drugs or new treatment strategies to improve the outcome of these patient...

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Main Authors: Chen Mei, Gaixiang Xu, Cuiping Zheng, Yaping Xie, Minming Li, Yanping Shao, Rongxin Yao, Shi Tao, Wei Jiang, Jun Guo, Zhiyin Zheng, Wei Wang, Xinping Zhou, Liya Ma, Li Ye, Yingwan Luo, Chunmei Yang, Wenjuan Yu, Wanzhuo Xie, Jie Jin, Hongyan Tong
Format: Article
Language:English
Published: Ferrata Storti Foundation 2025-06-01
Series:Haematologica
Online Access:https://haematologica.org/article/view/12102
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Summary:Erythropoiesis-stimulating agents (ESAs) achieve hematological improvement-erythroid (HIE) in only 30% of ESA-naïve lower risk myelodysplastic syndrome (LR-MDS) patients with anemia, highlighting the need for developing novel drugs or new treatment strategies to improve the outcome of these patients. We conducted this multicenter, single-arm trial to investigate the efficacy and safety of a triple regimen consisting of recombinant human erythropoietin (rhEPO), all-trans retinoic acid (ATRA) and testosterone undecanoate in patients with anemia due to lower-risk MDS based on Revised International Prognostic Scoring System. Eligible patients received rhEPO 10000 IU/day, oral ATRA 25 mg/m2/day and oral testosterone undecanoate 80 mg twice daily for 12 weeks. The primary endpoint was the proportion of patients achieving HI-E during 12 weeks of treatment. Of 52 eligible patients, 32 (61.5%, 95%CI 48.0%-73.5%) achieved HI-E, meeting the primary endpoint. Fifteen patients (65.2% [15/23]) with baseline serum erythropoietin ≤500 IU/L had HI-E versus 58.6% of those (17/29) with baseline serum erythropoietin >500 IU/L. More patients with very low or low risk had HI-E than those with intermediate risk (73.3% vs. 45.5%, P = 0.041) and fewer patients with mutated ASXL1 had HI-E than those with wildtype ASXL1 (33.3% vs. 70.0%, P = 0.040). The regimen had an acceptable safety profile compatible with individual agents. In conclusion, the triple regimen of rhEPO combined with ATRA and testosterone undecanoate attained HI-E in approximately 61.5% of patients regardless of baseline serum EPO levels, supporting further development of this regimen for LR-MDS patients with anemia. This study was registered at CHICTR.ORG.CN as ChiCTR2000032845.
ISSN:0390-6078
1592-8721