FLT3-ITD mutation

However, there is growing literature that patterns of co-mutation, and more importantly, postremission measurable residual disease (MRD) status, modify these risks dynamically; necessitating an adaptive approach to optimize patient outcomes. In this review, we summarize evidence on how molecular and MRD features could assist clinicians in identifying high-risk patients within these favorable-risk subgroups, and where escalation of therapy, including with allogeneic transplantation in first remission, may be beneficial.

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.

P3, N=106, Completed, Arog Pharmaceuticals, Inc. | Recruiting --> Completed | N=322 --> 106 | Trial completion date: Oct 2024 --> Apr 2026 | Trial primary completion date: Oct 2024 --> Apr 2026

P3, N=214, Completed, Arog Pharmaceuticals, Inc. | Recruiting --> Completed | N=510 --> 214 | Trial completion date: Nov 2024 --> Apr 2026 | Trial primary completion date: Nov 2022 --> Apr 2026

Our findings indicate that while relapse after allo-HCT in AML is genetically diverse, timing of recurrence remains the most critical determinant of outcome. Given that certain genetic changes may inform therapeutic options, these findings highlight the relevance of longitudinal molecular monitoring especially during the early post-transplant period.

P2, N=35, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

Since the IPSS-R and IPSS-M showed a poorly prognostic separation for MDS/AML patients, we further established a new prognostic model MDS/AML-IPSS-M and significantly improved its prognostic discrimination ability. Taking together, our research findings enhance the understanding of the molecular biology of MDS and can provide important guidance for the clinical identification of MDS/AML patients that might benefit clinical decision-making and therapeutic research.

P1/2, N=49, Recruiting, Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla | Not yet recruiting --> Recruiting

While subtypes of AML are increasingly defined by druggable driver mutations including FLT3-ITD, IDH1, IDH2, and NPM1, conventional chemotherapy and reduced intensity induction regimens (e.g., azacitidine-venetoclax) remain therapeutic backbones. Current understanding of AML biology and state-of-the-art tools for MRD measurement are reviewed here in an effort to promote clinical and laboratory investigator collaboration for the development of reliable tools for improving outcomes in this deadly disease. Clinical trial number: not applicable.

Among them, compound 35 showed the most potent inhibition against FLT3-ITD (IC₅₀ = 3.16 ± 0.49 nM) and FLT3-WT (IC₅₀ = 294.7 ± 14.5 nM), comparable to the clinical reference midostaurin, with a ∼93-fold selectivity index...Mechanistic studies demonstrated that compound 35 effectively suppressed FLT3 phosphorylation and downstream STAT5, Akt, and Erk signaling, induced G2/M cell-cycle arrest, and triggered apoptosis in FLT3-ITD-positive AML cells. Taken together, these findings identify compound 35 as a potent and selective FLT3 inhibitor and establish a promising scaffold for the development of next-generation therapeutics against FLT3-driven leukemias.

These results were confirmed in the CBF-2006 validation cohort. KIT-TKD mutations in RUNX1::RUNX1T1 and FLT3-ITD in CBFB::MYH11 worsen prognosis independently of MRD and must be included in risk stratification of CBF AMLs.