FLT3 mutation

P=N/A, N=111, Completed, The first affiliated hospital, Zhejiang University School of Medicine; The first affiliated hospital, Zhejiang University School of Medicine

Cells were treated with VEN, the MCL-1 inhibitor S63845 and the mitogen-activated protein kinase (MEK) inhibitor trametinib (TRA), alone or in combination. The presented results highlight the role of MAPK-driven MCL-1 and BCL(x)L expression, which mediates VEN resistance. While dual inhibition of B-cell lymphoma 2 and MCL-1 is already effective, additional MEK inhibition may further improve outcomes in PTPN11-mutated AML.

P1, N=30, Not yet recruiting, David Avigan

AML with HOXB3 hypomethylation usually has unique genetic patterns such as a normal karyotype, cytogenetic/molecular-intermediate risk, and mutations in FLT3-ITD, NPM1 and DNMT3A. Despite these associations, HOXB3 hypomethylation may serve as an independent prognostic biomarker for AML.

Five patients (8.8%) were refractory to induction therapy, and relapse occurred in 21.1% (12 patients). These findings support the effectiveness and acceptable tolerability of midostaurin in routine clinical practice for FLT3-mutated AML.

These results suggest an association of PRDM16 overexpression with the NPM1/FLT3-ITD/DNMT3A triple-mutant AML genotype, typically linked to high leukemia stem cell frequencies and poor prognosis. Importantly, within this adverse AML subtype low PRDM16 expression is an independent prognostic marker for favorable outcome, supporting an anti-leukemic mechanism in AMLs with repressed PRDM16 transcription.

Overall, dapolsertib demonstrated modest single-agent activity in patients with AML. This trial was registered at www.clinicaltrials.gov as #NCT03008187.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) showed the highest benefit in the NPM1-mut adverse-risk subgroup. The HARMONY classification provides the basis for a refined genetic risk stratification for adult NPM1-mut AML with potential clinical impact on allo-HSCT decision-making.

P1/2, N=73, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Jan 2028 | Trial primary completion date: Jan 2026 --> Jan 2028

P1/2, N=42, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Jan 2028 | Trial primary completion date: Jan 2026 --> Jan 2028

No new safety concerns were identified. Long-term gilteritinib treatment improved clinical outcomes compared with SC and was well-tolerated in a predominantly Asian population with relapsed/refractory FLT3-mutated AML.