Quizartinib 26.5mg tablets

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Approximately 30% of patients present alterations in the FMS-like receptor tyrosine kinase 3 (FLT3) gene, which are associated with poor prognosis. FLT3 inhibitors - midostaurin (first-generation), gilteritinib and quizartinib (second-generation) - have been developed to block FLT3 activation. Given the need of optimizing treatment in FLT3-mutated AML, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the safety profiles of FLT3 inhibitors. Following the PRISMA statement, we searched Embase, MEDLINE and Cochrane Library. The Cochrane Risk of Bias Tool for RCTs was used for quality assessment. Of 2132 references, seven RCTs, involving 2409 adult patients, met inclusion criteria: quizartinib and midostaurin in two trials each and gilteritinib in three. The most frequently reported adverse events (AEs) were classified under the System Organ Class (SOC) Blood and lymphatic system disorders (N = 5474, 58.4% of them related to FLT3 inhibitors). The most frequently observed non-hematological AEs were gastrointestinal disorders, pyrexia, elevated ALT/AST and headache. FLT3 inhibitors are not associated with a significant increase in the risk of AEs compared to standard treatments. No meaningful differences in AE risk were observed among the three drugs. The only exception was an higher risk of ALT increased with gilteritinib (RR = 2.40, 95% CI: 1.16-4.95). Future studies should stratify safety outcomes by demographic and clinical characteristics and incorporate long-term follow-up for a more comprehensive safety assessment in clinical practice.

Abstract licence: CC BY

Abstract FLT3-mutated acute myeloid leukemia (FLT3mut AML) is associated with poor outcomes. Although FLT3 inhibitors (FLT3is) combined with chemotherapy improve responses, long-term survival remains limited, and the optimal first-line strategy is unclear. We conducted a Bayesian network meta-analysis of eight randomized trials, including 1,793 patients, to compare intensive regimens for overall survival (OS). Treatments studied were 3 + 7 with midostaurin, quizartinib, sorafenib, gemtuzumab ozogamicin (GO), glasdegib, CPX-351, and decitabine. FLT3i-based regimens improved outcomes but showed attenuated effects in this analysis, consistent with prior data. The small population with FLT3 mutation treated with GO + 3 + 7 and CPX-351 provided good outcomes (SUCRA 86.1% and 71.7%), while glasdegib + 3 + 7 and decitabine resulted in less effective strategies. Notably, 3 + 7 + GO showed superior benefit despite limited FLT3mut subgroup evidence. Ongoing studies are exploring CPX-351, GO, and FLT3i combinations, as well as novel strategies. Prospective, mutation-specific trials are needed to define optimal therapy.

Abstract licence: CC BY