Avatrombopag is effective in patients with chemoradiotherapy-induced aplastic anemia: a single-center, retrospective study

Published:November 15, 2022DOI:


      • AVA showed acceptable effects on patients with secondary AA after chemoradiotherapy.
      • AVA showed a dose-dependent effect on patients.
      • Previous ELT and age had no effect on patients’ response to AVA.
      • Safety and effectiveness of AVA were further confirmed by this study.
      Aplastic anemia (AA) secondary to radiotherapy presents a difficult situation in the treatment of both the malignant tumor and AA itself. We aimed to evaluate the efficacy of avatrombopag (AVA), a thrombopoietin receptor agonist, in patients with AA secondary to chemoradiotherapy. In this retrospective study, patients with malignant tumors who were diagnosed with AA after radiotherapy and chemotherapy and accepted AVA between September 2020 and October 2021 at Peking Union Medical College Hospital were selected. A total of 34 patients were enrolled, including 13 (38.2%) men, with a median age of 60 (20–71) years. At a median of 8 (6–18) months of follow-up, the overall response rates (ORRs) at 1, 3, and 6 months were 32.4%, 55.9%, and 58.8%, respectively, and the complete response rates (CRRs) were 5.9%, 14.7%, and 23.5%, respectively. The median time to respond was 3 (1–6) months. In total, 15.0% of patients relapsed during follow-up, but no clonal evolution was noticed. Mild side effects were observed in 17.6% of patients without drug withdrawal. At the end of follow-up, 17.6% of patients had tumors relapsed. Four patients died, three from tumor relapse and one from cerebral hemorrhage. The ORR and CRR did not correlate with eltrombopag before AVA (p > 0.05) but increased when the total exposure of AVA increased (p = 0.011), and the threshold for AVA response was a cumulative dose > 3,000 mg (p = 0.013). AVA yielded good response and tolerance in patients treated for AA secondary to chemoradiotherapy, and a higher dose may correlate with better response.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Experimental Hematology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Killick SB
        • Bown N
        • Cavenagh J
        • et al.
        Guidelines for the diagnosis and management of adult aplastic anaemia.
        Br J Haematol. 2016; 172: 187-207
        • Peck-Radosavljevic M
        • Simon K
        • Iacobellis A
        • et al.
        Lusutrombopag for the treatment of thrombocytopenia in patients with chronic liver disease undergoing invasive procedures (L-PLUS 2).
        Hepatology. 2019; 70: 1336-1348
        • Georges GE
        • Doney K
        • Storb R.
        Severe aplastic anemia: allogeneic bone marrow transplantation as first-line treatment.
        Blood Adv. 2018; 2: 2020-2028
        • Townsley DM
        • Scheinberg P
        • Winkler T
        • et al.
        Eltrombopag added to standard immunosuppression for aplastic anemia.
        N Engl J Med. 2017; 376: 1540-1550
        • Babushok DV.
        Eltrombopag: a springboard to early responses in SAA.
        Blood. 2022; 139: 1-2
        • Patel BA
        • Groarke EM
        • Lotter J
        • et al.
        Long-term outcomes in patients with severe aplastic anemia treated with immunosuppression and eltrombopag: a phase 2 study.
        Blood. 2022; 139: 34-43
        • Desmond R
        • Townsley DM
        • Dumitriu B
        • et al.
        Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug.
        Blood. 2014; 123: 1818-1825
        • Virk ZM
        • Kuter DJ
        Al-Samkari H. An evaluation of avatrombopag for the treatment of thrombocytopenia.
        Expert Opin Pharmacother. 2021; 22: 273-280
        • Kuter DJ.
        The structure, function, and clinical use of the thrombopoietin receptor agonist avatrombopag.
        Blood Rev. 2021; 100909
        • Peffault De Latour R
        • Kulasekararaj A
        • Iacobelli S
        • et al.
        Eltrombopag added to immunosuppression in severe aplastic anemia.
        N Engl J Med. 2022; 386: 11-23
        • Scheinberg P.
        Acquired severe aplastic anaemia: how medical therapy evolved in the 20th and 21st centuries.
        Br J Haematol. 2021; 194: 954-969
        • Scheinberg P.
        Activity of eltrombopag in severe aplastic anemia.
        Blood Adv. 2018; 2: 3054-3062
        • Kong Z
        • Qin P
        • Xiao S
        • et al.
        A novel recombinant human thrombopoietin therapy for the management of immune thrombocytopenia in pregnancy.
        Blood. 2017; 130: 1097-1103
        • Terrault NA
        • Hassanein T
        • Howell CD
        • et al.
        Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure.
        J Hepatol. 2014; 61: 1253-1259
        • Kuter DJ
        • Allen LF.
        Avatrombopag, an oral thrombopoietin receptor agonist: results of two double-blind, dose-rising, placebo-controlled Phase 1 studies.
        Br J Haematol. 2018; 183: 466-478
        • Bussel JB
        • Kuter DJ
        • Aledort LM
        • et al.
        A randomized trial of avatrombopag, an investigational thrombopoietin-receptor agonist, in persistent and chronic immune thrombocytopenia.
        Blood. 2014; 123: 3887-3894
        • Ghanima W
        • Cooper N
        • Rodeghiero F
        • et al.
        Thrombopoietin receptor agonists: ten years later.
        Haematologica. 2019; 104: 1112-1123
        • Ikeda Y
        • Miyakawa Y.
        Development of thrombopoietin receptor agonists for clinical use.
        J Thromb Haemost. 2009; 7: 239-244
        • Luby TM
        • Baranwal A
        • Yang M
        • et al.
        AKR-501 activates the thrombopoietin receptor through interaction with the transmembrane domain.
        Blood. 2008; 112 (–5391): 5391
        • Jurczak W
        • Chojnowski K
        • Mayer J
        • et al.
        Phase 3 randomised study of avatrombopag, a novel thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia.
        Br J Haematol. 2018; 183: 479-490
        • Fukushima-Shintani M
        • Suzuki K
        • Iwatsuki Y
        • et al.
        AKR-501 (YM477) a novel orally-active thrombopoietin receptor agonist.
        Eur J Haematol. 2009; 82: 247-254
        • Al-Samkari H
        • Kuter DJ.
        Optimal use of thrombopoietin receptor agonists in immune thrombocytopenia.
        Ther Adv Hematol. 2019; 102040620719841735
        • Markham A.
        Avatrombopag: a review in thrombocytopenia.
        Drugs. 2021; 81: 1905-1913
      1. Sobi. FDA grants avatrombopag Orphan Drug Designation for the treatment of chemotherapy-induced thrombocytopenia. Available at: Accessed April 9, 2021.

        • Al-Samkari H
        • Kolb-Sielecki J
        • Safina SZ
        • et al.
        Avatrombopag for chemotherapy-induced thrombocytopenia in patients with non-haematological malignancies: an international, randomised, double-blind, placebo-controlled, phase 3 trial.
        Lancet Haematol. 2022; 9: e179-e189
        • Lozano ML
        • Rodeghiero F.
        Thrombopoietin receptor agonist in chemotherapy-induced thrombocytopenia.
        Lancet Haematol. 2022; 9: e168-e169
        • Terrault N
        • Chen YC
        • Izumi N
        • et al.
        Avatrombopag before procedures reduces need for platelet transfusion in patients with chronic liver disease and thrombocytopenia.
        Gastroenterology. 2018; 155: 705-718
        • Gao Y
        • Liu Q
        • Shen Y
        • et al.
        Effect of avatrombopag in the management of severe and refractory chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumors.
        Platelets. 2022; 33: 1024-1030
        • Winkler T
        • Fan X
        • Cooper J
        • et al.
        Treatment optimization and genomic outcomes in refractory severe aplastic anemia treated with eltrombopag.
        Blood. 2019; 133: 2575-2585
        • Fukushima-Shintani M
        • Suzuki K
        • Iwatsuki Y
        • et al.
        AKR-501 (YM477) in combination with thrombopoietin enhances human megakaryocytopoiesis.
        Exp Hematol. 2008; 36: 1337-1342
        • Al-Samkari H
        • Parnes AD
        • Goodarzi K
        • et al.
        A multicenter study of romiplostim for chemotherapy-induced thrombocytopenia in solid tumors and hematologic malignancies.
        Haematologica. 2021; 106: 1148-1157
        • Fattizzo B
        • Levati G
        • Cassin R
        • et al.
        Eltrombopag in immune thrombocytopenia, aplastic anemia, and myelodysplastic syndrome: from megakaryopoiesis to immunomodulation.
        Drugs. 2019; 79: 1305-1319
      2. Glaxosmithkline. Promacta: prescribing information. Available at: Accessed April 1, 2021.

        • Jenkins JM
        • Williams D
        • Deng Y
        • et al.
        Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist.
        Blood. 2007; 109: 4739-4741
        • Kumagai Y
        • Fujita T
        • Ozaki M
        • et al.
        Pharmacodynamics and pharmacokinetics of AMG 531, a thrombopoiesis-stimulating peptibody, in healthy Japanese subjects: a randomized, placebo-controlled study.
        J Clin Pharmacol. 2007; 47: 1489-1497
        • Erickson-Miller CL
        • Delorme E
        • Tian S-S
        • et al.
        Preclinical activity of eltrombopag (SB-497115), an oral, nonpeptide thrombopoietin receptor agonist.
        Stem Cells. 2009; 27: 424-430
        • Deng J
        • Hu H
        • Huang F
        • et al.
        Comparative efficacy and safety of thrombopoietin receptor agonists in adults with thrombocytopenia: a systematic review and network meta-analysis of randomized controlled trial.
        Front Pharmacol. 2021; 12704093
        • Li C
        • Li X
        • Huang F
        • et al.
        Efficacy and safety of avatrombopag in patients with thrombocytopenia: a systematic review and meta-analysis of randomized controlled trials.
        Front Pharmacol. 2019; 10: 829
        • Olnes MJ
        • Scheinberg P
        • Calvo KR
        • et al.
        Eltrombopag and improved hematopoiesis in refractory aplastic anemia.
        N Engl J Med. 2012; 367: 11-19