Eltrombopag for the treatment of inherited thrombocytopenias: a phase II clinical trial

Zaninetti, Carlo; Gresele, Paolo; Bertomoro, Antonella; Klersy, Catherine; Candia, Erica De; Veneri, Dino; Barozzi, Serena; Fierro, Tiziana; Alberelli, Maria Adele; Musella, Valeria; Noris, Patrizia; Fabris, Fabrizio; Balduini, Carlo L.; Pecci, Alessandro

doi:10.3324/haematol.2019.223966

Cited by 57 publications

(60 citation statements)

References 38 publications

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“…This finding suggests that short‐term eltrombopag administration can also be expected to help avoid or limit the use of platelet transfusions in preparation for the majority of elective surgical procedures in patients with ANKRD26 ‐RT or WAS/XLT. One enrolled patient with ITGA2B / ITGB3 ‐RT did not achieve a platelet response .…”

Section: Tpo‐rasmentioning

confidence: 99%

“…We started a phase I/II clinical trial (NCT02422394) in April 2015 to determine whether: (i) short‐term eltrombopag administration is effective in preparing patients with different forms of HTP for surgery or other invasive procedures; and (ii) long‐term eltrombopag administration can be used to stably reduce spontaneous bleeding for long periods of time in patients with clinically significant bleeding symptoms. The study recruited patients with MYH9 ‐RD, WAS/XLT, ANKRD26 ‐RT, monoallelic Bernard–Soulier syndrome (mBSS), and the form of HTP deriving from monoallelic mutations in ITGA2B or ITGB3 (integrin α IIb /integrin β 3 ‐related thrombocytopenia [ ITGA2B / ITGB3 ‐RT]) . Although patients with HTPs caused by mutations in GATA1 , GFI1B , TUBB1 , ACTN1 or CYCS were also eligible, enrollment was not possible, owing to the rarity of the disorders or the mild thrombocytopenia of affected patients.…”

Section: Tpo‐rasmentioning

confidence: 99%

“…In phase I of this study, eltrombopag (50 mg daily) is given for 3 weeks, and can be given for an additional 3 weeks at 75 mg daily if the platelet count is < 100 × 10 9 L –1 at the end of the first treatment period (short‐term administration). In phase II, patients with clinically significant spontaneous bleeding who responded to eltrombopag with no serious adverse events in phase I are treated with eltrombopag (12.5–75 mg daily) for 16 weeks (long‐term administration) . The trial was closed in April 2018.…”

Section: Tpo‐rasmentioning

confidence: 99%

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Thrombopoietin receptor agonists in hereditary thrombocytopenias

Rodeghiero

Pecci

Balduini

2018

Journal of Thrombosis and Haemostasis

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Hereditary thrombocytopenias (HTPs) constitute a heterogeneous group of diseases characterized by a reduction in platelet count and a potential bleeding risk. As a result of advances in diagnostic methods, HTPs are increasingly being identified, and appear to be less rare than previously thought. Most HTPs do not have effective treatments, except for platelet transfusion when bleeding occurs and in preparation for procedures associated with a risk of bleeding. Preliminary clinical evidence suggests that thrombopoietin receptor agonists (TPO-RAs) with an established use in the treatment of certain acquired thrombocytopenias are well tolerated and provide clinical benefits in patients with some forms of HTP. These drugs may therefore be considered for the treatment of HTPs in clinical practice. However, caution and close monitoring are recommended, owing to the absence of long-term safety data and the potential risks posed by prolonged bone marrow stimulation in certain HTPs. In this review, we summarize the available clinical data on TPO-RAs in the treatment of HTPs, and discuss their use in patients with these disorders. We believe that TPO-RAs will play a major role in the treatment of HTPs, particularly myosin heavy chain 9-related disease, Wiskott-Aldrich syndrome, X-linked thrombocytopenia, and thrombocytopenia caused by THPO mutations.

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Section: Tpo‐rasmentioning

confidence: 99%

Section: Tpo‐rasmentioning

confidence: 99%

Section: Tpo‐rasmentioning

confidence: 99%

See 1 more Smart Citation

Thrombopoietin receptor agonists in hereditary thrombocytopenias

Rodeghiero

Pecci

Balduini

2018

Journal of Thrombosis and Haemostasis

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“…However, especially in Glanzmann's thrombasthenia (GT), platelet transfusion should be restricted to situations in which other treatments fail to reduce the risk of alloimmunization of patients against the glycoprotein lacking on their own platelets. To transiently increase the platelet count, a thrombopoietin-receptor agonist (TPO-RA) may represent an alternative to platelet concentrates in a subgroup of IPDs [52,53]. Only in WAS, splenectomy represents an option to increase platelet count.…”

Section: Treatment Of Ipds Is Usually Symptomaticmentioning

confidence: 99%

Diagnosis of Inherited Platelet Disorders on a Blood Smear

Zaninetti

Greinacher

2020

JCM

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Inherited platelet disorders (IPDs) are rare diseases featured by low platelet count and defective platelet function. Patients have variable bleeding diathesis and sometimes additional features that can be congenital or acquired. Identification of an IPD is desirable to avoid misdiagnosis of immune thrombocytopenia and the use of improper treatments. Diagnostic tools include platelet function studies and genetic testing. The latter can be challenging as the correlation of its outcomes with phenotype is not easy. The immune-morphological evaluation of blood smears (by light- and immunofluorescence microscopy) represents a reliable method to phenotype subjects with suspected IPD. It is relatively cheap, not excessively time-consuming and applicable to shipped samples. In some forms, it can provide a diagnosis by itself, as for MYH9-RD, or in addition to other first-line tests as aggregometry or flow cytometry. In regard to genetic testing, it can guide specific sequencing. Since only minimal amounts of blood are needed for the preparation of blood smears, it can be used to characterize thrombocytopenia in pediatric patients and even newborns further. In principle, it is based on visualizing alterations in the distribution of proteins, which result from specific genetic mutations by using monoclonal antibodies. It can be applied to identify deficiencies in membrane proteins, disturbed distribution of cytoskeletal proteins, and alpha as well as delta granules. On the other hand, mutations associated with impaired signal transduction are difficult to identify by immunofluorescence of blood smears. This review summarizes technical aspects and the main diagnostic patterns achievable by this method.

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“…It is approved globally in immune thrombocytopenia. 1 The efficacy of eltrombopag in diseases not only characterised by isolated thrombocytopenia (chemotherapy-induced thrombocytopenia and inherited thrombocytopenia 2 ), but with pancytopenia-like aplastic anaemia (AA), 3 myelodysplastic syndromes (MDS) 4 and post-allogeneic transplant graft dysfunction, 5 have emerged over the last decade. Eltrombopag induces haematological responses in 40-50% of patients with AA refractory or relapsed following immunosuppressive therapy (IST) [6][7][8] and augments and hastens response in treatment-na€ ıve patients with AA whilst used with IST.…”

mentioning

confidence: 99%