Xospata (gilteritinib)

We experimentally validated several actionable findings, including tepotinib to target the IRAK1/4-cholesterol pathway in glioblastoma, brigatinib to target the MARK2/3-Hippo pathway in pancreatic cancer and gilteritinib to overcome MET mutation-driven drug resistance and metastasis. To facilitate exploration of our data, we provide KIRHub, a web-based tool that allows identification of existing inhibitors of wild-type and mutated kinases to guide precision oncology.

Subsequently, the CML burden declined as the AML clone regrew. This case highlights the importance of accurately assessing clonal changes using genetic analysis when implementing molecular targeted therapy for hematologic malignancies.

First-generation inhibitors, such as midostaurin, provided the foundation for targeted therapy, while recently developed agents such as gilteritinib and quizartinib have shown more selectivity and demonstrated superior clinical efficiency and improved tolerability. This review discusses the significance of FLT-3 mutations, the evolution of targeted therapies, current treatment guidelines, and ongoing challenges such as resistance and high relapse rates. We also discuss the emerging combinations of therapies and novel agents currently in clinical trials that aim to overcome resistance and improve long-term outcomes for patients with FLT-3-mutated AML.

In the subgroup analysis, post-HSCT gilteritinib showed an RFS benefit in cord blood transplantation (CBT; 79.4% vs. 26.1%, p < 0.001), but not in bone marrow or peripheral blood stem cell transplantation. This Japanese real-world study supports the tolerability and effectiveness of post-HSCT gilteritinib in R/R FLT3-mutated AML.

This case highlights potential ocular neurotoxicity associated with Gilteritinib, a targeted therapy not previously linked to corneal nerve dysfunction. Increased clinical awareness is recommended for ophthalmologists and hematologists managing patients with FLT3-mutated AML who are receiving targeted therapies.

Although the OS from diagnosis improved significantly in the FLT3i era, relapse after allo-HSCT remained a substantial challenge. Further studies are needed to optimize FLT3i maintenance therapy strategies.

Not available.

P1, N=40, Recruiting, Astellas Pharma Global Development, Inc.

In this first real-world analysis of post-alloHCT FLT3-TKI maintenance in older adults, utilization was low and adherence was modest, although not impaired by age alone. Gilteritinib demonstrated the highest adherence and appeared to have favorable tolerability. Strategies to improve adherence and prospective data in older adults are needed to maximize the benefits of FLT3-TKI maintenance in this population.

P1, N=18, Recruiting, Memorial Sloan Kettering Cancer Center | N=36 --> 18

Here, we detail the current targeted therapies available for AML: specifically, those targeting the BCL2 family (venetoclax), FLT3 (midostaurin, gilteritinib, quizartinib), IDH1/2 (enasidenib, ivosidenib), and MENIN (revumenib, ziftomenib). In addition, we outline potential mechanisms of resistance against these therapies, as well as efforts being taken to prevent or bypass them.