Summary

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• This summary is based on the review of five systematic review(s)/meta-analysis(es). ^[1-5]
• Overall Effectiveness of FMS-like tyrosine kinase 3 (FLT3) Inhibitors: FLT3 inhibitors demonstrated a relative risk (RR) of 1.11 for achieving complete remission (CR), with a confidence interval (CI) of 1.00 to 1.22, p = 0.05. The hazard ratio (HR) for overall survival (OS) was 0.83 (95% CI: 0.75 to 0.92, p = 0.0005), and for event-free survival (EFS), it was 0.85 (95% CI: 0.77 to 0.94, p = 0.002). Relapse-free survival (RFS) showed an HR of 0.76 (95% CI: 0.64 to 0.90, p = 0.001).
• Gilteritinib Effectiveness: In the ADMIRAL Trial, gilteritinib significantly improved overall survival and CR rates in relapsed/refractory acute myeloid leukemia (R/R AML) with manageable adverse effects. For FLT3 mutated R/R AML, median survival with gilteritinib was 9.3 months, with a transplant rate of 25.5%.
• Comparative Effectiveness: In the QuANTUM-R Trial, quizartinib suggested longer overall survival compared to standard chemotherapy, while midostaurin showed pooled effectiveness for OS, EFS, RFS, and CR when evaluated with other agents. Gemtuzumab Ozogamicin (GO) had a median survival of 13.8 months and a transplant rate of 19%.
• Adverse Events (AEs): Common adverse events associated with FLT3 inhibitors include gastrointestinal effects such as diarrhea, hand-foot syndrome, and nausea, as well as hematological issues including febrile neutropenia, anemia, and thrombocytopenia. FLT3 inhibitors were associated with a higher relative risk of grade 3 and above vascular, dermatological, respiratory, and hepatobiliary adverse events compared to control, although the actual numbers were small.
• Specific Safety Profiles: Gilteritinib demonstrated manageable adverse effects in the ADMIRAL Trial, while quizartinib raised concerns about cardiotoxicity in the QuANTUM-R Trial. Increased risks of thrombocytopenia, neutropenia, anemia, skin- and cardiac-related adverse effects, along with elevated alanine aminotransferase, cough, and dyspnea were noted across FLT3 inhibitors.
• Specific Populations and Subgroups: The findings emphasize improved outcomes in patients with FLT3 mutations, particularly AML, where FLT3 inhibitors lead to better prognosis both pre- and post-allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Second-generation FLT3 inhibitors, such as gilteritinib and quizartinib, show noted effectiveness in R/R AML, and gilteritinib demonstrates relative effectiveness for de novo R/R AML patients unfit for intensive chemotherapy, with ongoing trials addressing treatment strategies for older patients with AML.