Sequential Use of Romiplostim after Eltrombopag for Refractory Thrombocytopenia in Hydrocarbon-Induced Myelodysplasia

Luis F. Morales; Santiago J. Miyara; Sara Guevara; Christine N. Metz; Muhammad Shoaib; Stacey Watt; Stefanos Zafeiropoulos; Alexia McCann-Molmenti; Kei Hayashida; Ryosuke Takegawa; Koichiro Shinozaki; Rishabh C. Choudhary; Elena C. Brindley; Mitsuaki Nishikimi; Adam M. Kressel; Yaser M. Alsalmay; Elvio A. Mazzotta; Young Min Cho; Gabriel I. Aranalde; Daniel A. Grande; Stavros Zanos; Linda Shore-Lesserson; Lance B. Becker; Ernesto P. Molmenti

doi:10.1055/s-0041-1726366

International Journal of Angiology, Inhaltsverzeichnis

Int J Angiol 2024; 33(04): 318-321
DOI: 10.1055/s-0041-1726366

Rapid Communication

Sequential Use of Romiplostim after Eltrombopag for Refractory Thrombocytopenia in Hydrocarbon-Induced Myelodysplasia

Luis F. Morales^*

¹Department of Surgery, North Shore University Hospital, Manhasset, New York

,

Santiago J. Miyara ^*

²Elmezzi Graduate School of Molecular Medicine, Manhasset, New York

³Feinstein Institutes for Medical Research, Manhasset, New York

,

Sara Guevara^*

¹Department of Surgery, North Shore University Hospital, Manhasset, New York

,

Christine N. Metz

²Elmezzi Graduate School of Molecular Medicine, Manhasset, New York

³Feinstein Institutes for Medical Research, Manhasset, New York

,

Muhammad Shoaib

³Feinstein Institutes for Medical Research, Manhasset, New York

⁴Department of Emergency Medicine, North Shore University Hospital, Manhasset, New York

⁵Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York

,

Stacey Watt

⁶Jacobs School of Medicine and Biomedical Sciences, Buffalo, University at Buffalo, Buffalo, New York

,

Stefanos Zafeiropoulos

²Elmezzi Graduate School of Molecular Medicine, Manhasset, New York

³Feinstein Institutes for Medical Research, Manhasset, New York

,

Alexia McCann-Molmenti

¹Department of Surgery, North Shore University Hospital, Manhasset, New York

,

Kei Hayashida

³Feinstein Institutes for Medical Research, Manhasset, New York

⁴Department of Emergency Medicine, North Shore University Hospital, Manhasset, New York

,

Ryosuke Takegawa

³Feinstein Institutes for Medical Research, Manhasset, New York

⁴Department of Emergency Medicine, North Shore University Hospital, Manhasset, New York

,

Koichiro Shinozaki

³Feinstein Institutes for Medical Research, Manhasset, New York

⁴Department of Emergency Medicine, North Shore University Hospital, Manhasset, New York

,

Rishabh C. Choudhary

³Feinstein Institutes for Medical Research, Manhasset, New York

⁴Department of Emergency Medicine, North Shore University Hospital, Manhasset, New York

,

Elena C. Brindley

³Feinstein Institutes for Medical Research, Manhasset, New York

⁵Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York

,

Mitsuaki Nishikimi

³Feinstein Institutes for Medical Research, Manhasset, New York

⁴Department of Emergency Medicine, North Shore University Hospital, Manhasset, New York

,

Adam M. Kressel

¹Department of Surgery, North Shore University Hospital, Manhasset, New York

³Feinstein Institutes for Medical Research, Manhasset, New York

,

Yaser M. Alsalmay

¹Department of Surgery, North Shore University Hospital, Manhasset, New York

,

Elvio A. Mazzotta

⁷Department of Anesthesiology, The Wexner Medical Center, The Ohio State University, Columbus, Ohio

,

Young Min Cho

¹Department of Surgery, North Shore University Hospital, Manhasset, New York

³Feinstein Institutes for Medical Research, Manhasset, New York

,

Gabriel I. Aranalde

¹Department of Surgery, North Shore University Hospital, Manhasset, New York

,

Daniel A. Grande

²Elmezzi Graduate School of Molecular Medicine, Manhasset, New York

³Feinstein Institutes for Medical Research, Manhasset, New York

⁵Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York

,

Stavros Zanos

²Elmezzi Graduate School of Molecular Medicine, Manhasset, New York

³Feinstein Institutes for Medical Research, Manhasset, New York

,

Linda Shore-Lesserson

⁵Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York

⁸Department of Anesthesiology, North Shore University Hospital, Manhasset, New York

,

Lance B. Becker

¹Department of Surgery, North Shore University Hospital, Manhasset, New York

²Elmezzi Graduate School of Molecular Medicine, Manhasset, New York

³Feinstein Institutes for Medical Research, Manhasset, New York

⁵Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York

,

Ernesto P. Molmenti

¹Department of Surgery, North Shore University Hospital, Manhasset, New York

³Feinstein Institutes for Medical Research, Manhasset, New York

⁴Department of Emergency Medicine, North Shore University Hospital, Manhasset, New York

⁵Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York

› Institutsangaben

Abstract

We describe the clinical course of a 65-year-old male patient who suffered from hydrocarbon-induced myelodysplasia and was successfully treated with the thrombopoietin receptor agonist (TPO-RA), romiplostim. Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis, cytopenias, and increased risk of leukemic transformation. Here, we present a clinical vignette of MDS-associated thrombocytopenia refractory to first-line drugs as well as the TPO-RA, eltrombopag. To date, romiplostim is an U.S. Food and Drug Administration (FDA)-approved drug for idiopathic thrombocytopenic purpura and thrombocytopenia secondary to liver disease. Of note, currently the FDA advises against its use in MDS based on previous long-term safety concerns. Since the therapeutic options for thrombocytopenia in MDS patients are sparse, repurposing and reassessing romiplostim in this setting have been the focus of recent studies. At the time of writing, no published double-blind randomized clinical trials have conducted a head-to-head comparison between romiplostim and eltrombopag in thrombocytopenic MDS patients. To the best of our knowledge, for a thrombocytopenic patient in the setting of MDS, this is the first documented report of refractory clinical response after a 2-year use of eltrombopag in which replacement of treatment with romiplostim resulted in sustained physiological counts of thrombocytes within four weeks.

Keywords

romiplostim - myelodysplastic syndromes - thrombopoietin receptor agonist - thrombopoiesis - thrombocytopenia - eltrombopag

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Referenzen

References
1 Will B, Zhou L, Vogler TO. et al. Stem and progenitor cells in myelodysplastic syndromes show aberrant stage-specific expansion and harbor genetic and epigenetic alterations. Blood 2012; 120 (10) 2076-2086
2 Pang WW, Pluvinage JV, Price EA. et al. Hematopoietic stem cell and progenitor cell mechanisms in myelodysplastic syndromes. Proc Natl Acad Sci U S A 2013; 110 (08) 3011-3016
3 Cazzola M. Myelodysplastic syndromes. N Engl J Med 2020; 383 (14) 1358-1374
4 Dayyani F, Conley AP, Strom SS. et al. Cause of death in patients with lower-risk myelodysplastic syndrome. Cancer 2010; 116 (09) 2174-2179
5 Schnatter AR, Glass DC, Tang G, Irons RD, Rushton L. Myelodysplastic syndrome and benzene exposure among petroleum workers: an international pooled analysis. J Natl Cancer Inst 2012; 104 (22) 1724-1737
6 Rushton L, Schnatter AR, Tang G, Glass DC. Acute myeloid and chronic lymphoid leukaemias and exposure to low-level benzene among petroleum workers. Br J Cancer 2014; 110 (03) 783-787
7 Verma DK, des Tombe K. Benzene in gasoline and crude oil: occupational and environmental implications. AIHA J (Fairfax, Va) 2002; 63 (02) 225-230
8 Loomis D, Guyton KZ, Grosse Y. et al; International Agency for Research on Cancer Monograph Working Group. Carcinogenicity of benzene. Lancet Oncol 2017; 18 (12) 1574-1575
9 Mason LH, Harp JP, Han DY. Pb neurotoxicity: neuropsychological effects of lead toxicity. BioMed Res Int 2014; 2014: 840547
10 Le QH, Tran DD, Chen YC, Nguyen HL. Risk of lead exposure from transport stations to human health: a case study in the highland province of Vietnam. Toxics 2019; 7 (03) 48
11 Aoki T, Harada Y, Matsubara E. et al. Thrombopoietin receptor agonists in refractory immune thrombocytopenia: differential responses to eltrombopag and romiplostim: a case report and possible explanations. J Clin Pharm Ther 2012; 37 (06) 729-732
12 González-Porras JR, Mingot-Castellano ME, Andrade MM. et al. Use of eltrombopag after romiplostim in primary immune thrombocytopenia. Br J Haematol 2015; 169 (01) 111-116
13 Piccin A, Amaddii G, Natolino F, Billio A, Cortelazzo S. Idiopathic thrombocytopenic purpura resistant to eltrombopag, but cured with romiplostim. Blood Transfus 2014; 12 (1, suppl 1): s149-s150
14 Kuter DJ, Bussel JB, Lyons RM. et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet 2008; 371 (9610): 395-403
15 Zhang J, Liang Y, Ai Y. et al. Eltrombopag versus romiplostim in treatment of adult patients with immune thrombocytopenia: a systematic review incorporating an indirect-comparison meta-analysis. PLoS One 2018; 13 (06) e0198504
16 Bussel JB, Buchanan GR, Nugent DJ. et al. A randomized, double-blind study of romiplostim to determine its safety and efficacy in children with immune thrombocytopenia. Blood 2011; 118 (01) 28-36
17 Moussa MM, Mowafy N. Preoperative use of romiplostim in thrombocytopenic patients with chronic hepatitis C and liver cirrhosis. J Gastroenterol Hepatol 2013; 28 (02) 335-341
18 Afdhal NH, Dusheiko GM, Giannini EG. et al. Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV infection and cirrhosis, allowing for effective antiviral therapy. Gastroenterology 2014; 146 (02) 442-52.e1
19 Dusheiko G, Afdhal NH, Giannini E. et al. Final results of open-label treatment with eltrombopag during ENABLE 1: a study of eltrombopag as an adjunct for antiviral treatment of hepatitis C virus associated with thrombocytopenia. . Hepatology 2011
20 Solar GP, Kerr WG, Zeigler FC. et al. Role of c-mpl in early hematopoiesis. Blood 1998; 92 (01) 4-10
21 Debili N, Wendling F, Cosman D. et al. The Mpl receptor is expressed in the megakaryocytic lineage from late progenitors to platelets. Blood 1995; 85 (02) 391-401
22 Kantarjian H, O'Brien S, Ravandi F. et al. Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original International Prognostic Scoring System. Cancer 2008; 113 (06) 1351-1361
23 Kantarjian H, Giles F, List A. et al. The incidence and impact of thrombocytopenia in myelodysplastic syndromes. Cancer 2007; 109 (09) 1705-1714
24 Hofmann WK, Koeffler HP. Myelodysplastic syndrome. Annu Rev Med 2005; 56: 1-16
25 D'Arena G, Guariglia R, Mansueto G. et al. No cross-resistance after sequential use of romiplostim and eltrombopag in chronic immune thrombocytopenic purpura. [published correction appears in Blood. 2014 Mar 20;123(12):1971. Dosage error in article text] Blood 2013; 121 (07) 1240-1242
26 Rusnak DW, Rudolph SK, Safavi A, Erickson-Miller CL. Eltrombopag, but not romiplostim or thrombopoietin, inhibits growth of thrombopoietin receptor positive and negative human leukemia cell lines. Blood 2012; 120 (02) 386-394
27 Stasi R, Evangelista ML, Amadori S. Novel thrombopoietic agents: a review of their use in idiopathic thrombocytopenic purpura. Drugs 2008; 68 (07) 901-912
28 Raslova H, Vainchenker W, Plo I. Eltrombopag, a potent stimulator of megakaryopoiesis. Haematologica 2016; 101 (12) 1443-1445
29 Giagounidis A, Mufti GJ, Fenaux P. et al. Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1-risk myelodysplastic syndrome and thrombocytopenia. Cancer 2014; 120 (12) 1838-1846