Severe Gastrointestinal Toxicity Following the Use of Gilteritinib: A Case Series and Analysis of Postmarketing Surveillance Data

Abstract

Gilteritinib has been approved as monotherapy in adults with acute myeloid leukemia (AML) FLT3 mutated with relapsed or refractory disease, in light of its advantages in terms of survival and the favorable safety profile. Hepatobiliary disorders and musculoskeletal and connective tissue disorders represent the most frequent adverse reactions associated with gilteritinib, whereas the most frequent serious adverse reaction is acute kidney injury. In the summary of product characteristics, gastrointestinal (GI) events are indicated as very common, in particular diarrhea, nausea and stypsis. Furthermore, serious GI disorders have been observed with gilteritinib in clinical trials, including GI hemorrhage, GI perforation and GI obstruction. However, the association with the FLT3 inhibitor has not been confirmed. Nevertheless, serious GI AEs have been recognized as an important potential risk to be monitored in postmarketing surveillance. We present three cases of serious self-limiting GI events observed in patients on gilteritinib treatment for AML, and an analysis of relevant available postmarketing surveillance data.

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

“…Gilteritinib may also directly affect platelet functions and indirectly megakaryocytes [ 18 ]. Twenty-two percent of patients treated with this drug developed thrombocytopenia [ 4 ], and gastrointestinal bleeding has been reported in animal models and in the AZA/gilteritinib trial [ 7 , 19 ]. The drug may also exert a direct action on the brain vasculature.…”

“…In this analysis, conducted among 107 patients, 77.6% of patients presented an AE, but only 9.3% were hemorrhagic complications. Bleeding events of grade ≥3 were reported in 7% of patients experiencing an AE [ 6 ], and an Italian series reported 3 cases of gastrointestinal bleeding [ 7 ]. We describe the clinical history of five patients from three Italian institutions treated with gilteritinib for R/R FLT3-mutated AML, who developed ICH soon after exposure to the drug (some characteristics of these patients are summarized in Table 1 ).…”