Immunotherapy with Monoclonal Antibodies for Acute Myeloid Leukemia: A Work in Progress.

In the last few years, molecularly targeted agents and immune-based treatments (ITs) have significantly changed the landscape of anti-cancer therapy. Indeed, ITs have been proven to be very effective when used against metastatic solid tumors, for which outcomes are extremely poor when using standard approaches. Such a scenario has only been partially reproduced in hematologic malignancies. In the context of acute myeloid leukemia (AML), as innovative drugs are eagerly awaited in the relapsed/refractory setting, different ITs have been explored, but the results are still unsatisfactory. In this work, we will discuss the most important clinical studies to date that adopt ITs in AML, providing the basis to understand how this approach, although still in its infancy, may represent a promising therapeutic tool for the future treatment of AML patients.

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

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.