The role of romiplostim for pediatric patients with immune thrombocytopenia

Al‐Samkari, Hanny; Grace, Rachael F.; Kuter, David J.

doi:10.1177/2040620720912992

Cited by 19 publications

(12 citation statements)

References 70 publications

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“…Earlier studies had reported a higher immunogenicity incidence in pediatric compared with adult populations; with anti-romiplostim binding antibodies occurring in 8% versus 4% of patients and anti-romiplostim neutralizing antibodies in 3% versus < 1%. 11,24 However, in an analysis that evaluated romiplostim immunogenicity in adults with ITP in 13 clinical trials, 20 reported incidence of anti-romiplostim binding antibodies was 6.2% (60/961 patients), similar to the 8.9% incidence observed in our pediatric ITP analysis. Incidence of anti-romiplostim neutralizing antibodies was 0.4% in the adult ITP analysis 20 and 2.9% in our pediatric ITP analysis.…”

Section: Discussionsupporting

confidence: 69%

Assessment of romiplostim immunogenicity in pediatric patients in clinical trials and in a global postmarketing registry

et al. 2021

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Development of first-generation thrombopoietins (TPOs) was halted due to antibodies that neutralized endogenous TPO, causing protracted thrombocytopenia in some patients. The second-generation TPO receptor agonist romiplostim, having no homology to TPO, was developed to circumvent potential immunogenicity. We examined development of binding and neutralizing antibodies to romiplostim and TPO among pediatric patients with primary immune thrombocytopenia (ITP) in 5 trials and a global postmarketing registry. In the trials, 25/280 (8.9%) patients developed anti-romiplostim binding antibodies. The first positive result was detected 67 weeks (median) after starting romiplostim; median romiplostim dose was 8 µg/kg and median platelet count 87 x 109/L. Most patients who developed anti-romiplostim binding antibodies (18/25 [72%]) had ≥ 90% platelet assessments showing response. Anti-romiplostim neutralizing antibodies developed in 8/280 (2.9%) patients; this was unrelated to romiplostim dose, and most patients who developed anti-romiplostim neutralizing antibodies (7/8 [88%]) had platelet response. Nine of 279 (3.2%) patients developed anti-TPO binding antibodies, and 1 (0.4%) developed transient anti-TPO neutralizing antibodies. In 8 patients who developed anti-romiplostim neutralizing antibodies, no TPO cross-reactivity was observed. In the postmarketing registry, 3/19 (15.8%) patients had anti-romiplostim binding antibodies; 1 (5.3%) had anti-romiplostim neutralizing antibodies. These results show that immunogenicity to romiplostim occurs infrequently in children with ITP and is generally not associated with loss of platelet response or other negative clinical sequelae.

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Section: Discussionsupporting

confidence: 69%

Assessment of romiplostim immunogenicity in pediatric patients in clinical trials and in a global postmarketing registry

et al. 2021

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“…63 Though romiplostim does not have the ease of administration as oral TPO-RAs, a recent study has found that self-administration of romiplostim by patients did not increase adverse events compared with administration by healthcare professionals. 64,65 Eltrombopag is a small molecule TPO-RA approved by the US FDA for ITP following the failure of a first-line treatment and is initiated orally at a dose of 50 mg daily in adults (or 25 mg daily in patients of East Asian descent), titrated to a maximum dose of 75 mg daily to reach a goal platelet count of 50-200 x 10 9 /L. 66 Multiple studies have found eltrombopag significantly increases platelet response (59-79%) with less bleeding (statistically significant OR 0.49) and reduced use of concomitant ITP treatment.…”

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confidence: 99%

Management of Adult Patients with Immune Thrombocytopenia (ITP): A Review on Current Guidance and Experience from Clinical Practice

Song¹,

Al‐Samkari²

2021

JBM

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Immune thrombocytopenia (ITP) is an autoimmune process resulting in increased destruction and inadequate production of platelets that can result in bleeding, fatigue, and reduced health-related quality of life. While treatment is not required for many patients with ITP, the occurrence of bleeding manifestations, severe thrombocytopenia, and requirement for invasive procedures are among the reasons necessitating initiation of therapy. Corticosteroids, intravenous immunoglobulin, and anti-RhD immune globulin are typical first-line and rescue treatments, but these agents typically do not result in a durable remission in adult patients. Most patients requiring treatment therefore require subsequent line therapies, such as thrombopoietin receptor agonists (TPO-RAs), rituximab, fostamatinib, splenectomy, or a number of other immunosuppressive agents. In this focused review, we discuss management of adult ITP in the acute and chronic settings.

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“…Romiplostim is a synthetic polypeptide that activates downstream signals and stimulates platelet production by binding to the TPO-R on MKs (81). A multicenter study of romiplostim for chemotherapy-induced thrombocytopenia was conducted in solid tumors and hematological malignancies; the results demonstrated that 71% of patients responded to romiplostim and weekly dosing was found to be superior to intracycle dosing (82).…”

Section: Promotion Of Platelet Productionmentioning

confidence: 99%

Developments in the production of platelets from stem cells (Review)

et al. 2020

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Platelets are small pieces of cytoplasm that have become detached from the cytoplasm of mature megakaryocytes (MKs) in the bone marrow. Platelets modulate vascular system integrity and serve important role, particularly in hemostasis. With the rapid development of clinical medicine, the demand for platelet transfusion as a life-saving intervention increases continuously. Stem cell technology appears to be highly promising for transfusion medicine, and the generation of platelets from stem cells would be of great value in the clinical setting. Furthermore, several studies have been undertaken to investigate the potential of producing platelets from stem cells. Initial success has been achieved in terms of the yields and function of platelets generated from stem cells. However, the requirements of clinical practice remain unmet. The aim of the present review was to focus on several sources of stem cells and factors that induce MK differentiation. Updated information on current research into the genetic regulation of megakaryocytopoiesis and platelet generation was summarized. Additionally, advanced strategies of platelet generation were reviewed and the progress made in this field was discussed.

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The role of romiplostim for pediatric patients with immune thrombocytopenia

Cited by 19 publications

References 70 publications

Assessment of romiplostim immunogenicity in pediatric patients in clinical trials and in a global postmarketing registry

Assessment of romiplostim immunogenicity in pediatric patients in clinical trials and in a global postmarketing registry

Management of Adult Patients with Immune Thrombocytopenia (ITP): A Review on Current Guidance and Experience from Clinical Practice

Developments in the production of platelets from stem cells (Review)

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