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

Abstract

SummaryThrombopoietin 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.

Early immunomodulation in immune thrombocytopenia—A report of the ICIS meeting in Lenzerheide, Switzerland 2022

“…In their hypothesis, cytokine alterations that occur in ITP crisis could be reversed after treatment with TPO‐RA, that is, an increase in TGFβ, IL‐4 and IL‐10 and a decrease in Il‐2, IL‐17 and IFNγ. However, Lucchini et al 77 observed some contrary results in the ESTIT trial, including a decrease in IL4, IL10 and TNFα in patients who responded to eltrombopag, so as Schifferli et al that reported a decrease of nearly all cytokines except TGF‐β and IL‐35 in the iROM pilot study 88 …”

“…In 2022, the iROM study enrolled 13 patients to describe the immunological pattern leading to TFR after 22 weeks of romiplostim administration 88 . Patients included were exposed to first‐line treatment only; nine of them were newly diagnosed and four had chronic ITP.…”

“…In 2022, the iROM study enrolled 13 patients to describe the immunological pattern leading to TFR after 22 weeks of romiplostim administration. 88 Patients included were exposed to first-line treatment only; nine of them were newly diagnosed and four had chronic ITP. The trial demonstrated that six of nine (66%) patients with newly diagnosed ITP achieved a complete sustained remission (platelet count ≥100 × 10 9 /L) at 1 year without the need for additional treatments beyond 22 weeks in comparison with none of the four patients with chronic ITP at study inclusion.…”

“…However, Lucchini et al 77 observed some contrary results in the ESTIT trial, including a decrease in IL4, IL10 and TNFα in patients who responded to eltrombopag, so as Schifferli et al that reported a decrease of nearly all cytokines except TGF-β and IL-35 in the iROM pilot study. 88 So, why does remission occur? Several responses (alone or combined) may appear in addressing this issue.…”

Update on the Use of Thrombopoietin-Receptor Agonists in Pediatrics

“…[88][89][90][91][92] Growing evidence suggests that TPO-RAs support or even induce SROT in adult ITP. 88,93 For adults with primary ITP ( 6 months of disease) showing an insufficient response to first-line treatments like corticosteroids and immunoglobulins, a multicenter phase 2 RCT demonstrated treatmentfree remission (platelets >50/nL) in 32% of patients for at least 6 months posttreatment. 94 This led to the FDA approval for extending romiplostim use as first-line treatment in newly diagnosed adult ITP.…”