Gilteritinib is currently approved for patients with relapsed/refractory AML with FLT3 mutations, based on the positive results of the pivotal ADMIRAL study. In ADMIRAL trial, no increased risk of bleeding was reported, but in the previous dose finding study, a single event of intracranial hemorrhage (ICH) was registered after exposure to subtherapeutic doses of gilteritinib. Here, we report the first case series on five ICHs diagnosed in patients with FLT3-mutated AML, occurred within the first month of exposure to gilteritinib. Our cohort included 24 patients treated in three Italian centers. Most of these ICH cases were non-severe and self-limiting, while one was fatal. This link with ICHs remains in any case uncertain for the presence of active AML. We further reported that an analysis of the post-marketing surveillance data (EudraVigilance) retrieved other 11 cases of ICHs present in the database after gilteritinib treatment. A causality assessment was performed according to the Dx3 method to evaluate the possibility that ICHs might be an actual side effect of gilteritinib. In conclusion, further research is needed to elucidate the potential role of gilteritinib in the pathogenesis of ICHs.

Perrone, S., Imperatore, S., Sucato, G., Notarianni, E., Corbingi, A., Andriola, C., et al. (2023). Gilteritinib and the risk of intracranial hemorrhage: a case series of a possible, under-reported side effect. ANNALS OF HEMATOLOGY [10.1007/s00277-023-05392-2].

Gilteritinib and the risk of intracranial hemorrhage: a case series of a possible, under-reported side effect

Napolitano, Mariasanta;
2023-08-22

Abstract

Gilteritinib is currently approved for patients with relapsed/refractory AML with FLT3 mutations, based on the positive results of the pivotal ADMIRAL study. In ADMIRAL trial, no increased risk of bleeding was reported, but in the previous dose finding study, a single event of intracranial hemorrhage (ICH) was registered after exposure to subtherapeutic doses of gilteritinib. Here, we report the first case series on five ICHs diagnosed in patients with FLT3-mutated AML, occurred within the first month of exposure to gilteritinib. Our cohort included 24 patients treated in three Italian centers. Most of these ICH cases were non-severe and self-limiting, while one was fatal. This link with ICHs remains in any case uncertain for the presence of active AML. We further reported that an analysis of the post-marketing surveillance data (EudraVigilance) retrieved other 11 cases of ICHs present in the database after gilteritinib treatment. A causality assessment was performed according to the Dx3 method to evaluate the possibility that ICHs might be an actual side effect of gilteritinib. In conclusion, further research is needed to elucidate the potential role of gilteritinib in the pathogenesis of ICHs.
22-ago-2023
Perrone, S., Imperatore, S., Sucato, G., Notarianni, E., Corbingi, A., Andriola, C., et al. (2023). Gilteritinib and the risk of intracranial hemorrhage: a case series of a possible, under-reported side effect. ANNALS OF HEMATOLOGY [10.1007/s00277-023-05392-2].
File in questo prodotto:
File Dimensione Formato  
Articolo gilteritinib.pdf

accesso aperto

Descrizione: articolo pubblicata
Tipologia: Versione Editoriale
Dimensione 644.92 kB
Formato Adobe PDF
644.92 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/608237
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 0
social impact