Review Article

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Blood Res 2022; 57(S1):

Published online April 30, 2022

https://doi.org/10.5045/br.2022.2022038

© The Korean Society of Hematology

Recent advances in treatments of adult immune thrombocytopenia

Dae Sik Kim

Division of Hematology-Oncology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea

Correspondence to : Dae Sik Kim, M.D., Ph.D.
Division of Hematology-Oncology, Department of Internal Medicine, Korea University Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul 08308, Korea
E-mail: kay9801@naver.com

Received: February 8, 2022; Revised: April 15, 2022; Accepted: April 21, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Immune thrombocytopenia (ITP) is isolated thrombocytopenia characterized by autoimmune-mediated disruption of platelet without other etiologies. Treatments for chronic ITP consist of corticosteroids, intravenous immunoglobulins, anti-D immunoglobulin, rituximab, thrombopoietin receptor agonists, immunosuppressants and splenectomy. Although current therapies are effective in over two-thirds of patients, some patients are refractory to therapies or fail to achieve long-term responses. Recently, great advance has been made in identifying various mechanisms involved in ITP pathogenesis, and new treatments targeting these pathways are being developed. Novel agents such as splenic tyrosine kinase inhibitor, Bruton kinase inhibitor, plasma cell targeting therapies, neonatal Fc receptor inhibitor, platelet desialylation inhibitor, and inhibition of the classical complement pathway are expected to be effective for ITP treatment. This review summarizes current strategies and emerging therapies of ITP.

Keywords Immune thrombocytopenia, Platelet, Treatment, Pathogenesis, Thrombopoietin receptor agonist

Article

Review Article

Blood Res 2022; 57(S1): S112-S119

Published online April 30, 2022 https://doi.org/10.5045/br.2022.2022038

Copyright © The Korean Society of Hematology.

Recent advances in treatments of adult immune thrombocytopenia

Dae Sik Kim

Division of Hematology-Oncology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea

Correspondence to:Dae Sik Kim, M.D., Ph.D.
Division of Hematology-Oncology, Department of Internal Medicine, Korea University Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul 08308, Korea
E-mail: kay9801@naver.com

Received: February 8, 2022; Revised: April 15, 2022; Accepted: April 21, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Immune thrombocytopenia (ITP) is isolated thrombocytopenia characterized by autoimmune-mediated disruption of platelet without other etiologies. Treatments for chronic ITP consist of corticosteroids, intravenous immunoglobulins, anti-D immunoglobulin, rituximab, thrombopoietin receptor agonists, immunosuppressants and splenectomy. Although current therapies are effective in over two-thirds of patients, some patients are refractory to therapies or fail to achieve long-term responses. Recently, great advance has been made in identifying various mechanisms involved in ITP pathogenesis, and new treatments targeting these pathways are being developed. Novel agents such as splenic tyrosine kinase inhibitor, Bruton kinase inhibitor, plasma cell targeting therapies, neonatal Fc receptor inhibitor, platelet desialylation inhibitor, and inhibition of the classical complement pathway are expected to be effective for ITP treatment. This review summarizes current strategies and emerging therapies of ITP.

Keywords: Immune thrombocytopenia, Platelet, Treatment, Pathogenesis, Thrombopoietin receptor agonist

Fig 1.

Figure 1.Treatment approach of immune thrombocytopenia.
Blood Research 2022; 57: S112-S119https://doi.org/10.5045/br.2022.2022038

Table 1 . Novel therapies for treatment of immune thrombocytopenia..

TargetDrug classMechanismAgentsDevelopment status
MacrophageSyk inhibitorDecrease in ADCP (inhibition of macrophage phagocytosis)FostamatinibApproved (US)
MacrophageBTK inhibitorDecrease in ADCP (inhibition of macrophage phagocytosis)RilzabrutinibPhase 3 (NCT04562766)
Plasma cellsProteasome inhibitorInhibits plasma cell production of anti-platelet antibodyBortezomibPhase 1 (NCT03013114)
KZR-616Phase 1 (NCT04039477) withdrawn
Plasma cellsAnti-CD38 antibodyInhibits plasma cell production of anti-platelet antibodyDaratumumabPhase 2 (NCT04703621)
MezagitamabPhase 2 (NCT04278924)
Antiplatelet antibodiesFcRn blockerIncrease clearance of anti-platelet antibodyEfgartigimodPhase 2 (NCT03102593
RozanolixizumabPhase 3 (NCT00718692)
PlateletNeuraminidase inhibitorDecrease in platelet desialylation thus reducing their destruction in the liverOseltamivirPhase 2 (NCT01965626)
Classical complement pathwayC1s inhibitorDecrease in CDC (antibody inhibits C1s activity)SutimlimabPhase 2 (NCT04669600)

Abbreviations: ADCP, antibody-dependent cellular cytotoxicity; BTK, Bruton tyrosine kinase; CD, cluster of differentiation; CDC, complement-dependent cytotoxicity; FcRn, Neonatal Fc receptor; Syk, spleen tyrosine kinase..


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