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
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
Affiliations
Chen Mei
Myelodysplastic Syndromes Diagnosis and Therapy Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang
Gaixiang Xu
Myelodysplastic Syndromes Diagnosis and Therapy Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang
Cuiping Zheng
Department of hematology, Wenzhou Central Hospital, Wenzhou, Zhejiang
Yaping Xie
Department of Hematology, Hangzhou First People's Hospital, Hangzhou, Zhejiang
Minming Li
Department of Hematology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong
Yanping Shao
Department of Hematology, Taizhou Hospital of Zhejiang Province Affiliated with Wenzhou Medical University, Taizhou, Zhejiang
Rongxin Yao
Department of Hematology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang
Shi Tao
Department of Hematology, Shaoxing Second Hospital, Shaoxing, Zhejiang
Wei Jiang
Department of Hematology, Shangyu People's Hospital of Shaoxing, Shaoxing, Zhejiang
Jun Guo
Department of Hematology, Changxing County People's Hospital, Huzhou, Zhejiang
Zhiyin Zheng
Department of Haematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang
Wei Wang
Myelodysplastic Syndromes Diagnosis and Therapy Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang
Xinping Zhou
Myelodysplastic Syndromes Diagnosis and Therapy Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang
Liya Ma
Myelodysplastic Syndromes Diagnosis and Therapy Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang
Li Ye
Myelodysplastic Syndromes Diagnosis and Therapy Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang
Yingwan Luo
Myelodysplastic Syndromes Diagnosis and Therapy Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang
Chunmei Yang
Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang
Wenjuan Yu
Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang
Wanzhuo Xie
Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang
Jie Jin
Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang
Hongyan Tong
Myelodysplastic Syndromes Diagnosis and Therapy Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang
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.
