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Minerva Med ; 111(5): 467-477, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32955827

RESUMEN

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy, characterized by poor prognosis if treated with conventional therapy. Allogenic hematologic stem cell transplant can improve survival and can be curative, but it is available in a small percentage of patients given that the median age at diagnosis is 70 years. In this scenario it is assumed that only the development of precision medicine-driven therapy will change BPDCN patient prognosis. CD123 (the α-subunit of interleukin (IL)-3 receptor) is over-expressed on BPDCN cells surface and seems to be the ideal marker to develop antibody-based therapies. Tagraxofusp (Elzonris®), a recombinant immunotoxin consisting of human interleukin-3 fused to a truncated diphtheria toxin, has been approved by FDA in December 2018 for the treatment of BPDCN in adult and pediatric patients. tagraxofusp has shown promising clinical activity, with a high overall response rate and quite manageable safety profile even in elderly patients. It seems to improve overall survival too, but comparative trials are necessary to confirm this. Adverse events are commonly reported and the most important are transaminitis, thrombocytopenia and capillary leak syndrome (CLS). Therefore, to prevent the onset of severe CLS is recommended to reserve tagraxofusp for patients with preserved hepatic and cardiac functions, and to strictly observe serum albumin level. Further studies are required to resolve many several unanswered questions about tagraxofusp. In this review, we will resume and discuss pharmacological characteristic of tagraxofusp, results of clinical trials leading to its approval by FDA in 2018 and future perspectives about its use in BPDCN and other hematological malignancies.


Asunto(s)
Células Dendríticas , Neoplasias Hematológicas/tratamiento farmacológico , Subunidad alfa del Receptor de Interleucina-3/antagonistas & inhibidores , Medicina de Precisión , Proteínas Recombinantes de Fusión/farmacología , Anciano , Síndrome de Fuga Capilar/inducido químicamente , Síndrome de Fuga Capilar/prevención & control , Niño , Aprobación de Drogas , Evaluación Preclínica de Medicamentos , Etiquetado de Medicamentos , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/patología , Humanos , Pronóstico , Proteínas Recombinantes de Fusión/efectos adversos , Trombocitopenia/inducido químicamente , Transaminasas/sangre
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