Immunomodulation with romiplostim as a second‐line strategy in primary immune thrombocytopenia: The iROM study

Thrombopoietin receptor agonists (TPO‐RAs) stimulate platelet production, which might restore immunological tolerance in primary immune thrombocytopenia (ITP). The iROM study investigated romiplostim's immunomodulatory effects. Thirteen patients (median age, 31 years) who previously received fi...

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Published in:British journal of haematology 2023-10, Vol.203 (1), p.119-130
Main Authors: Schifferli, Alexandra, Rüfer, Axel, Rovo, Alicia, Nimmerjahn, Falk, Cantoni, Nathan, Holbro, Andreas, Favre, Geneviève, Dirks, Jan, Wieland, Anna, Faeth, Heike, Pereira, Renata, Kühne, Thomas
Format: Article
Language:English
Subjects:
Autoimmunity
Foxp3 protein
GATA-3 protein
Gene expression
Hematology
Idiopathic thrombocytopenic purpura
Immune system
Immunological tolerance
Immunology
Immunomodulation
Lymphocytes T
Patients
Platelets
Remission
Thrombocytopenia
Thrombopoietin
Titration
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Summary:Thrombopoietin receptor agonists (TPO‐RAs) stimulate platelet production, which might restore immunological tolerance in primary immune thrombocytopenia (ITP). The iROM study investigated romiplostim's immunomodulatory effects. Thirteen patients (median age, 31 years) who previously received first‐line treatment received romiplostim for 22 weeks, followed by monitoring until week 52. In addition to immunological data, secondary end‐points included the sustained remission off‐treatment (SROT) rate at 1 year, romiplostim dose, platelet count and bleedings. Scheduled discontinuation of romiplostim and SROT were achieved in six patients with newly diagnosed ITP, whereas the remaining seven patients relapsed. Romiplostim dose titration was lower and platelet count response was stronger in patients with SROT than in relapsed patients. In all patients, regulatory T lymphocyte (Treg) counts increased until study completion and the counts were higher in patients with SROT. Interleukin (IL)‐4, IL‐9 and IL‐17F levels decreased significantly in all patients. FOXP3 (Treg), GATA3 (Th2) mRNA expression and transforming growth factor‐β levels increased in patients with SROT. Treatment with romiplostim modulates the immune system and possibly influences ITP prognosis. A rapid increase in platelet counts is likely important for inducing immune tolerance. Better outcomes might be achieved at an early stage of autoimmunity, but clinical studies are needed for confirmation.
ISSN:0007-1048
1365-2141
DOI:10.1111/bjh.19074