Eltrombopag is effective in patients with relapse/refractory aplastic anemia-report from a single center in China.
Adolescent
Adult
Aged
Aged, 80 and over
Anemia, Aplastic
/ diagnosis
Benzoates
/ therapeutic use
China
/ epidemiology
Female
Follow-Up Studies
Hospitals, University
Humans
Hydrazines
/ therapeutic use
Male
Middle Aged
Pyrazoles
/ therapeutic use
Recurrence
Retrospective Studies
Treatment Outcome
Young Adult
Aplastic anemia
Efficacy
Eltrombopag
Real-world study
Safety
Journal
Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
31
03
2020
accepted:
07
09
2020
pubmed:
19
9
2020
medline:
15
12
2020
entrez:
18
9
2020
Statut:
ppublish
Résumé
Eltrombopag has shown a promising effect on patients with refractory/relapsed aplastic anemia (AA). However, data in Asian patients are limited due to the short launching time. Data from relapsed/refractory AA patients treated with eltrombopag in Peking Union Medical College Hospital from December 2017 to May 2019 were analyzed retrospectively. Totally 41 patients including 37 non-severe AA and 4 severe AA were analyzed with a median age of 47 (13~81) years old. The dosage of eltrombopag varies from 25 mg every other day (qod) to 100 mg every day (qd) (median 75 mg qd) with the duration of 13 (3~23) months. The overall response rates were 51.2%, 58.5%, and 55.2% at 3-month, 6-month, and 1-year follow-up. Seventy-five percent of patients achieved the best response below the dosage of 75 mg qd at 3 (1-6) months. Two patients stopped eltrombopag after achieving complete remission and remained stable. Two patients relapsed and evolved to myelodysplastic syndrome. Adverse events included gastrointestinal discomfort, hepatic toxicity, and skin reactions, which were mild and controllable. Eltrombopag is effective for Chinese relapsed/refractory AA patients with a relatively lower dose and acceptable side effects.
Identifiants
pubmed: 32944791
doi: 10.1007/s00277-020-04266-1
pii: 10.1007/s00277-020-04266-1
doi:
Substances chimiques
Benzoates
0
Hydrazines
0
Pyrazoles
0
eltrombopag
S56D65XJ9G
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2755-2761Subventions
Organisme : Natural Science Foundation of Beijing Municipality
ID : 7192168
Organisme : Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences and Peking Union Medical College (CN)
ID : 2016-I2M-3-004
Organisme : the National Key Research and Development Program of China
ID : 2016YFC0901500
Commentaires et corrections
Type : ErratumIn
Références
Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, Hillmen P, Ireland R, Kulasekararaj A, Mufti G, Snowden JA, Samarasinghe S, Wood A, Marsh JC (2016) Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol 172(2):187–207. https://doi.org/10.1111/bjh.13853
doi: 10.1111/bjh.13853
pubmed: 26568159
Gill H, Wong RSM, Kwong YL (2017) From chronic immune thrombocytopenia to severe aplastic anemia: recent insights into the evolution of eltrombopag. Ther Adv Hematol 8(5):159–174. https://doi.org/10.1177/2040620717693573
doi: 10.1177/2040620717693573
pubmed: 28473904
pmcid: 5407506
Fattizzo B, Levati G, Cassin R, Barcellini W (2019) Eltrombopag in immune thrombocytopenia, aplastic anemia, and myelodysplastic syndrome: from megakaryopoiesis to immunomodulation. Drugs 79(12):1305–1319. https://doi.org/10.1007/s40265-019-01159-0
doi: 10.1007/s40265-019-01159-0
pubmed: 31292909
Desmond R, Townsley DM, Dumitriu B, Olnes MJ, Scheinberg P, Bevans M, Parikh AR, Broder K, Calvo KR, Wu CO, Young NS, Dunbar CE (2014) Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood 123(12):1818–1825. https://doi.org/10.1182/blood-2013-10-534743
doi: 10.1182/blood-2013-10-534743
pubmed: 24345753
pmcid: 3962161
Scheinberg P (2018) Activity of eltrombopag in severe aplastic anemia. Blood Adv 2(21):3054–3062. https://doi.org/10.1182/bloodadvances.2018020248
doi: 10.1182/bloodadvances.2018020248
pubmed: 30425070
pmcid: 6234374
Zhao Z, Sun Q, Sokoll LJ, Streiff M, Cheng Z, Grasmeder S, Townsley DM, Young NS, Dunbar CE, Winkler T (2018) Eltrombopag mobilizes iron in patients with aplastic anemia. Blood 131(21):2399–2402. https://doi.org/10.1182/blood-2018-01-826784
doi: 10.1182/blood-2018-01-826784
pubmed: 29632023
pmcid: 5969382
Olnes MJ, Scheinberg P, Calvo KR, Desmond R, Tang Y, Dumitriu B, Parikh AR, Soto S, Biancotto A, Feng X, Lozier J, Wu CO, Young NS, Dunbar CE (2012) Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med 367(1):11–19. https://doi.org/10.1056/NEJMoa1200931
doi: 10.1056/NEJMoa1200931
pubmed: 22762314
pmcid: 3422737
Geng W, Kearney S, Nelson S (2018) Upfront eltrombopag monotherapy induces stable hematologic remission in pediatric patients with nonsevere idiopathic aplastic anemia. Pediatr Blood Cancer 65(10):e27290. https://doi.org/10.1002/pbc.27290
doi: 10.1002/pbc.27290
pubmed: 29932285
Fattizzo B, Kulasekararaj AG, Hill A, Benson-Quarm N, Griffin M, Munir T, Arnold L, Riley K, Ireland R, De Lavallade H, Potter V, Consonni D, Hillmen P, Mufti GJ, Barcellini W, Marsh JCW (2019) Clinical and morphological predictors of outcome in older aplastic anemia patients treated with eltrombopag. Haematologica 104(11):e494–e496. https://doi.org/10.3324/haematol.2019.216374
doi: 10.3324/haematol.2019.216374
pubmed: 30890599
pmcid: 6821617
Cheng H, Wang X, Zhou D, Cao J, Larochelle A, Xu KL (2019) Eltrombopag combined with cyclosporine may have an effect on very severe aplastic anemia. Ann Hematol 98(8):2009–2011. https://doi.org/10.1007/s00277-019-03658-2
doi: 10.1007/s00277-019-03658-2
pubmed: 30891613
pmcid: 6855301
Desmond R, Townsley DM, Dunbar C, Young NS (2015) Eltrombopag in aplastic anemia. Semin Hematol 52(1):31–37. https://doi.org/10.1053/j.seminhematol.2014.10.002
doi: 10.1053/j.seminhematol.2014.10.002
pubmed: 25578417
Ecsedi M, Lengline E, Knol-Bout C, Bosman P, Eikema DJ, Afanasyev B, Maschan A, Dreger P, Halkes CJM, Drexler B, Cortelezzi A, Drenou B, Patriarca A, Bruno B, Onofrillo D, Lanino E, Pulanic D, Serventi-Seiwerth R, Garnier A, Ljungman P, Bonifazi F, Giammarco S, Tournilhac O, Pioltelli P, Rovo A, Risitano AM, de Latour RP, Dufour C, Passweg J (2019) Use of eltrombopag in aplastic anemia in Europe. Ann Hematol 98(6):1341–1350. https://doi.org/10.1007/s00277-019-03652-8
doi: 10.1007/s00277-019-03652-8
pubmed: 30915499
Hwang YY, Gill H, Chan TSY, Leung GMK, Cheung CYM, Kwong YL (2018) Eltrombopag in the management of aplastic anaemia: real-world experience in a non-trial setting. Hematology (Amsterdam, Netherlands) 23(7):399–404. https://doi.org/10.1080/10245332.2017.1422306
doi: 10.1080/10245332.2017.1422306
Konishi A, Nakaya A, Fujita S, Satake A, Nakanishi T, Azuma Y, Tsubokura Y, Saito R, Hotta M, Yoshimura H, Ishii K, Ito T, Nomura S (2019) Evaluation of eltrombopag in patients with aplastic anemia in real-world experience. Leuk Res Rep 11:11–13. https://doi.org/10.1016/j.lrr.2019.03.002
doi: 10.1016/j.lrr.2019.03.002
pubmed: 30911464
pmcid: 6416522
Yamazaki H, Ohta K, Iida H, Imada K, Obara N, Tokumine Y, Tomiyama Y, Usuki K, Imajo K, Miyamura K, Sasaki O, Fanghong Z, Hattori T, Tajima T, Matsuda A, Nakao S (2019) Hematologic recovery induced by eltrombopag in Japanese patients with aplastic anemia refractory or intolerant to immunosuppressive therapy. Int J Hematol 110(2):187–196. https://doi.org/10.1007/s12185-019-02683-1
doi: 10.1007/s12185-019-02683-1
pubmed: 31183813
Camitta BM, Rappeport JM, Parkman R, Nathan DG (1975) Selection of patients for bone marrow transplantation in severe aplastic anemia. Blood 45(3):355–363
doi: 10.1182/blood.V45.3.355.355
Marsh JC, Ball SE, Cavenagh J, Darbyshire P, Dokal I, Gordon-Smith EC, Keidan J, Laurie A, Martin A, Mercieca J, Killick SB, Stewart R, Yin JA (2009) Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol 147(1):43–70. https://doi.org/10.1111/j.1365-2141.2009.07842.x
doi: 10.1111/j.1365-2141.2009.07842.x
pubmed: 19673883
Townsley DM, Scheinberg P, Winkler T, Desmond R, Dumitriu B, Rios O, Weinstein B, Valdez J, Lotter J, Feng X, Desierto M, Leuva H, Bevans M, Wu C, Larochelle A, Calvo KR, Dunbar CE, Young NS (2017) Eltrombopag added to standard immunosuppression for aplastic anemia. N Engl J Med 376(16):1540–1550. https://doi.org/10.1056/NEJMoa1613878
doi: 10.1056/NEJMoa1613878
pubmed: 28423296
pmcid: 5548296
Matthys G, Park JW, McGuire S, Wire MB, Bowen C, Williams D, Jenkins J, Peng B (2011) Clinical pharmacokinetics, platelet response, and safety of eltrombopag at supratherapeutic doses of up to 200 mg once daily in healthy volunteers. J Clin Pharmacol 51(3):301–308. https://doi.org/10.1177/0091270010368677
doi: 10.1177/0091270010368677
pubmed: 20418510
Gibiansky E, Zhang J, Williams D, Wang Z, Ouellet D (2011) Population pharmacokinetics of eltrombopag in healthy subjects and patients with chronic idiopathic thrombocytopenic purpura. J Clin Pharmacol 51(6):842–856
doi: 10.1177/0091270010375427
Alexander WS, Roberts AW, Nicola NA, Li R, Metcalf D (1996) Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietic receptor c-Mpl. Blood 87(6):2162–2170
doi: 10.1182/blood.V87.6.2162.bloodjournal8762162
Qian H, Buza-Vidas N, Hyland CD, Jensen CT, Antonchuk J, Mansson R, Thoren LA, Ekblom M, Alexander WS, Jacobsen SEW Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells. Cell Stem Cell 1(6):671–684
Groarke EM, Patel BA, Diamond C, Gutierrez-Rodrigues F, Young NS (2019) Outcomes in pediatric patients with severe aplastic anemia treated with standard immunosuppression and eltrombopag. Blood 134(Supplement_1):454–454
doi: 10.1182/blood-2019-124811
Ho C, Visintini S (2018) CADTH rapid response reports. In: Eltrombopag for the treatment of aplastic anemia: a review of clinical and cost-effectiveness. Canadian Agency for Drugs and Technologies in Health Copyright (c) 2018 Canadian Agency for Drugs and Technologies in Health., Ottawa (ON)
Hong Y, Li X, Wan B, Li N, Chen Y (2019) Efficacy and safety of eltrombopag for aplastic anemia: a systematic review and meta-analysis. Clin Drug Investig 39(2):141–156. https://doi.org/10.1007/s40261-018-0725-2
doi: 10.1007/s40261-018-0725-2
pubmed: 30406906
Lum SH, Grainger JD (2016) Eltrombopag for the treatment of aplastic anemia: current perspectives. Drug Des Dev Ther 10:2833–2843. https://doi.org/10.2147/dddt.s95715
doi: 10.2147/dddt.s95715
Cooper JN, Young NS (2017) Clonality in context: hematopoietic clones in their marrow environment. Blood 130(22):2363–2372. https://doi.org/10.1182/blood-2017-07-794362
doi: 10.1182/blood-2017-07-794362
pubmed: 29046282
pmcid: 5709788