Drugs and Clinic Practice

Efficacy and safety of Roxadustat in the treatment of refractory NSAA and low-risk MDS-related anemia

  • Qinglin HU ,
  • Ziqi WAN ,
  • Chen YANG ,
  • Miao CHEN ,
  • Bing HAN
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  • Department of Hematology,Peking Union Medical College Hospital,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100730,China

Received date: 2023-12-22

  Online published: 2024-06-14

Abstract

Objective To investigate the overall and subgroup efficacy, subgroup differences, predictors of efficacy and safety of roxadustat in the treatment of refractory non-severe aplastic anemia (NSAA) and low-risk myelodysplastic syndromes (LR-MDS). Methods Patients with refractory NSAA and LR-MDS who were admitted to the Department of Hematology, Peking Union Medical College Hospital from August 2020 to December 2022 were enrolled. All patients received first-line standard treatment, including recombinant human erythropoietin (rhEPO) for at least 3 months before roxadustat treatment. All patients received roxadustat 2.5 mg/kg every other day for at least 3 months, and were followed up for at least 8 months. The clinical characteristics of patients, roxadustat efficacy, predictors of efficacy, adverse effects,relapse and disease clonal evolution were analyzed. Results A total of 40 patients including 24 refractory NSAA and 16 LR-MDS were included. median age was 56 (18 ~ 81) years and 40% were males. 65% of the patients were transfusion dependent. Median follow-up was 21 (9 ~ 34) months. 22.5%, 25.0%, 47.5% , 55.0%, 57.5%, 60.0% and 50.0% of the patients achieved haematological improvement-erythroid (HI-E) at months 1, 2, 3, 4, 5, 6, and end of the follow-up period, respectively, and no factors affecting HI-E were identified.The hemoglobin change from baseline was statistically different between the two groups at the end of the follow-up period. 50% of patients were relieved from transfusion dependence. Adverse reactions were reported in 22.5% of patients. 28.5% of patients relapsed after achieving HI-E, with a median time to relapse of 7(4 ~ 12) months. No clonal evolution was observed at the end of the follow-up period. Conclusions Our preliminary findings suggested that Roxadustat may be effective for patients with NSAA or LR-MDS refractory to conventional therapies and rhEPO, with mild adverse effects and low relapse rate.The degree of hemoglobin improvement may be better in the refractory NSAA patients.

Cite this article

Qinglin HU , Ziqi WAN , Chen YANG , Miao CHEN , Bing HAN . Efficacy and safety of Roxadustat in the treatment of refractory NSAA and low-risk MDS-related anemia[J]. The Journal of Practical Medicine, 2024 , 40(12) : 1719 -1724 . DOI: 10.3969/j.issn.1006-5725.2024.12.018

References

1 SACKEYFIO A, LOPES R D, KOVESDY C P, et al. Comparison of outcomes on hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) in anaemia associated with chronic kidney disease: network meta-analyses in dialysis and non-dialysis dependent populations [J]. Clin Kidney J, 2024, 17(1): sfad298. doi:10.1093/ckj/sfad298
2 SUGAHARA M, TANAKA T, NANGAKU M. Future perspectives of anemia management in chronic kidney disease using hypoxia-inducible factor-prolyl hydroxylase inhibitors [J]. Pharmacol Ther, 2022, 239: 108272. doi:10.1016/j.pharmthera.2022.108272
3 ZHANG Y, HE Y, WANG S, et al. Transfusion-dependent non-severe aplastic anemia: characteristics and outcomes in the clinic [J]. Front Immunol, 2023, 14: 1197982. doi:10.3389/fimmu.2023.1197982
4 BAZINET A, BRAVO G M. New Approaches to Myelodysplastic Syndrome Treatment [J]. Curr Treat Options Oncol, 2022, 23(5): 668-687. doi:10.1007/s11864-022-00965-1
5 CAMITTA B M, THOMAS E D, NATHAN D G, et al. Severe aplastic anemia: a prospective study of the effect of early marrow transplantation on acute mortality[J]. Blood, 1976,48(1):63-70 [J]. Blood, 2016, 128(18): 2191. doi:10.1182/blood.v48.1.63.63
6 中华医学会血液学分会. 骨髓增生异常综合征中国诊断与治疗指南(2019年版) [J]. 中华血液学杂志, 2019,40(2): 89-97. doi:10.3760/cma.j.issn.0253-2727.2019.02.001
7 GARCIA-MANERO G. Myelodysplastic syndromes: 2023 update on diagnosis, risk-stratification, and management [J]. Am J Hematol, 2023, 98(8): 1307-1325. doi:10.1002/ajh.26984
8 YOUNG N S. Aplastic Anemia [J]. N Engl J Med, 2018, 379(17): 1643-1656. doi:10.1056/nejmra1413485
9 BACIGALUPO A. How I treat acquired aplastic anemia [J]. Blood, 2017, 129(11): 1428-1436. doi:10.1182/blood-2016-08-693481
10 PALACIOS-BERRAQUERO M L, ALFONSO-PIéROLA A. Current Therapy of the Patients with MDS: Walking towards Personalized Therapy [J]. J Clin Med, 2021, 10(10):2107. doi:10.3390/jcm10102107
11 ISIDORI A, BORIN L, ELLI E, et al. Iron toxicity-Its effect on the bone marrow [J]. Blood Rev, 2018, 32(6): 473-479. doi:10.1016/j.blre.2018.04.004
12 TEICHMAN J, GEDDES M, ZHU N, et al. High transferrin saturation predicts inferior clinical outcomes in patients with myelodysplastic syndromes [J]. Haematologica, 2023, 108(2): 532-542. doi:10.3324/haematol.2022.280723
13 CHANG H, HE G, FU R, et al. Efficacy and safety of eltrombopag in Chinese patients with refractory or relapsed severe aplastic anemia [J]. Sci Rep, 2023, 13(1): 18955. doi:10.1038/s41598-023-45607-0
14 WANG C, SALLMAN D A. Current Therapeutic Landscape in Lower Risk Myelodysplastic Syndromes [J]. Curr Treat Options Oncol, 2023, 24(5): 387-408. doi:10.1007/s11864-023-01062-7
15 FENAUX P, PLATZBECKER U, MUFTI G J, et al. Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes [J]. N Engl J Med, 2020, 382(2): 140-151.
16 PLATZBECKER U, SANTINI V, KOMROKJI R S, et al. Long-term utilization and benefit of luspatercept in transfusion-dependent, erythropoiesis-stimulating agent-refractory or -intolerant patients with lower-risk myelodysplastic syndromes with ring sideroblasts [J]. Leukemia, 2023, 37(11): 2314-2318. doi:10.1038/s41375-023-02031-7
17 张玉培,谢新生,石雅洁,等. 异基因造血干细胞移植治疗ASXL1基因突变的骨髓增生异常综合征患者的效果[J]. 实用医学杂志, 2023, 39(23): 3087-3092. doi:10.3969/j.issn.1006-5725.2023.23.011
18 REN S, YAO X, LI Y, et al. Efficacy and safety of hypoxia-inducible factor-prolyl hydroxylase inhibitor treatment for anemia in chronic kidney disease: an umbrella review of meta-analyses [J]. Front Pharmacol, 2023, 14: 1296702. doi:10.3389/fphar.2023.1296702
19 HENRY D H, GLASPY J, HARRUP R, et al. Roxadustat for the treatment of anemia in patients with lower-risk myelodysplastic syndrome: Open-label, dose-selection, lead-in stage of a phase 3 study [J]. Am J Hematol, 2022, 97(2): 174-184. doi:10.1002/ajh.26397
20 OGAWA C, TSUCHIYA K, MAEDA K. Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors and Iron Metabolism [J]. Int J Mol Sci, 2023, 24(3):3037. doi:10.3390/ijms24033037
21 ZHAO J, XU Y, XIE J, et al. Roxadustat Does Not Affect Platelet Production, Activation, and Thrombosis Formation [J]. Arterioscler Thromb Vasc Biol, 2021, 41(10): 2523-2537. doi:10.1161/atvbaha.121.316495
22 MIES A, PLATZBECKER U. Increasing the effectiveness of hematopoiesis in myelodysplastic syndromes: erythropoiesis-stimulating agents and transforming growth factor-β superfamily inhibitors [J]. Semin Hematol, 2017, 54(3): 141-146. doi:10.1053/j.seminhematol.2017.06.004
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