Blood Res.  2021 Jun;56(2):102-108. 10.5045/br.2021.2021086.

Lenalidomide for anemia correction in lower-risk del(5q) myelodysplastic syndrome patients of Asian ethnicity

• Hong J
• Lee YJ
• Bae SH
• Yi JH
• Park S
• Chang MH
• Park YH
• Hyun SY
• Chung JS
• Jang JE
• Jung JY
• Jeon SY
• Song SY
• Kim H
• Kim DS
• Kim SH
• Kim MK
• Han SH
• Park S
• Kim YJ
• Lee JH
• on behalf of the AML/MDS Working Party of the Korean Society of Hematology

• KMID: 2517065
• DOI: http://doi.org/10.5045/br.2021.2021086

Abstract

Background
To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea.
Methods
Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed.
Results
A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%).
Conclusion
Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.

Keyword

5q deletion syndrome; Myelodysplastic syndrome; Lenalidomide; Anemia

Figure

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  Fig. 1 Hemoglobin level changes in responders after lenalidomide treatment (mean±SEM).

Reference

1. Cazzola M. 2020; Myelodysplastic syndromes. N Engl J Med. 3833:1358–74. DOI: 10.1056/NEJMra1904794. PMID: 32997910.

2. Greenberg P, Cox C, LeBeau MM, et al. 1997; International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 89:2079–88. DOI: 10.1182/blood.V89.6.2079. PMID: 9058730.

3. Greenberg PL, Tuechler H, Schanz J, et al. 2012; Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 120:2454–65. DOI: 10.1182/blood-2012-03-420489. PMID: 22740453. PMCID: PMC4425443.

4. Fenaux P, Adès L. 2013; How we treat lower-risk myelodysplastic syndromes. Blood. 121:4280–6. DOI: 10.1182/blood-2013-02-453068. PMID: 23575446.

5. Choi EJ, Lee JH, Lee JH, et al. 2018; Treatment and clinical outcomes of patients relapsing after allogeneic hematopoietic cell transplantation for myelodysplastic syndrome. Blood Res. 53:288–93. DOI: 10.5045/br.2018.53.4.288. PMID: 30588465. PMCID: PMC6300680.

6. Haase D. 2008; Cytogenetic features in myelodysplastic syndromes. Ann Hematol. 87:515–26. DOI: 10.1007/s00277-008-0483-y. PMID: 18414863. PMCID: PMC2413090.

7. Adema V, Bejar R. 2013; What lies beyond del(5q) in myelodysplastic syndrome? Haematologica. 98:1819–21. DOI: 10.3324/haematol.2013.094912. PMID: 24323981. PMCID: PMC3856955.

8. Arber DA, Orazi A, Hasserjian R, et al. 2016; The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 127:2391–405. DOI: 10.1182/blood-2016-03-643544. PMID: 27069254.

9. Boultwood J, Pellagatti A, McKenzie AN, Wainscoat JS. 2010; Advances in the 5q-syndrome. Blood. 116:5803–11. DOI: 10.1182/blood-2010-04-273771. PMID: 20733155. PMCID: PMC4450650.

10. Sperling AS, Gibson CJ, Ebert BL. 2017; The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia. Nat Rev Cancer. 17:5–19. DOI: 10.1038/nrc.2016.112. PMID: 27834397. PMCID: PMC5470392.

11. List A, Dewald G, Bennett J, et al. 2006; Lenalidomide in the myelo-dysplastic syndrome with chromosome 5q deletion. N Engl J Med. 355:1456–65. DOI: 10.1056/NEJMoa061292. PMID: 17021321.

12. Fenaux P, Giagounidis A, Selleslag D, et al. 2011; A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q. Blood. 118:3765–76. DOI: 10.1182/blood-2011-01-330126. PMID: 21753188.

13. Kuendgen A, Lauseker M, List AF, et al. 2013; Lenalidomide does not increase AML progression risk in RBC transfusion-dependent patients with Low- or Intermediate-1-risk MDS with del(5q): a comparative analysis. Leukemia. 27:1072–9. DOI: 10.1038/leu.2012.369. PMID: 23257782. PMCID: PMC3650492.

14. Lee JH, Lee JH, Shin YR, et al. 2003; Application of different prognostic scoring systems and comparison of the FAB and WHO classifications in Korean patients with myelodysplastic syndrome. Leukemia. 17:305–13. DOI: 10.1038/sj.leu.2402798. PMID: 12592327.

15. Miyazaki Y, Tuechler H, Sanz G, et al. 2018; Differing clinical features between Japanese and Caucasian patients with myelodysplastic syndromes: analysis from the International Working Group for Prognosis of MDS. Leuk Res. 73:51–7. DOI: 10.1016/j.leukres.2018.08.022. PMID: 30219650.

16. Harada H, Watanabe M, Suzuki K, et al. 2009; Lenalidomide is active in Japanese patients with symptomatic anemia in low- or intermediate-1 risk myelodysplastic syndromes with a deletion 5q abnormality. Int J Hematol. 90:353–60. DOI: 10.1007/s12185-009-0400-8. PMID: 19705057.

17. Kelaidi C, Park S, Brechignac S, et al. 2008; Treatment of myelo-dysplastic syndromes with 5q deletion before the lenalidomide era; the GFM experience with EPO and thalidomide. Leuk Res. 32:1049–53. DOI: 10.1016/j.leukres.2007.11.037. PMID: 18191202.

18. Pan WH, Flegal KM, Chang HY, Yeh WT, Yeh CJ, Lee WC. 2004; Body mass index and obesity-related metabolic disorders in Taiwanese and US whites and blacks: implications for definitions of overweight and obesity for Asians. Am J Clin Nutr. 79:31–9. DOI: 10.1093/ajcn/79.1.31. PMID: 14684394.

19. Le Bras F, Sebert M, Kelaidi C, et al. 2011; Treatment by lenalidomide in lower risk myelodysplastic syndrome with 5q deletion--the GFM experience. Leuk Res. 35:1444–8. DOI: 10.1016/j.leukres.2011.05.034. PMID: 21715006.

20. Hong J, Lee JH, Yhim HY, et al. 2018; Incidence of venous thrombo-embolism in Korea from 2009 to 2013. PLoS One. 13:e0191897. DOI: 10.1371/journal.pone.0191897. PMID: 29370290. PMCID: PMC5785001.