KMT2A rearrangement

The 11q23 rearrangement ALL with non-KMT2A::AFF1 transcript is mainly KMT2A::MLLT1, T-ALL is more common, and the rate of chromosomal karyotype detection is relatively low. Persistent positive KMT2A-r is unfavorable for patient survival, and allo-HSCT during the CR1 period may improve patient survival.

P1, N=29, Not yet recruiting, Children's Oncology Group

We next assessed ziftomenib against four MEN1 (gene encoding menin) mutants (T349M, M327I, G331R, G331D) associated with clinical resistance to another menin inhibitor revumenib. The crystal structures of ziftomenib in complex with menin wild-type, T349M or G331R mutants revealed a similar binding mode of ziftomenib to these menin variants, rationalizing potent inhibitory activity towards these mutants. Ziftomenib has recently received FDA approval for adult patients with NPM1-mutated acute myeloid leukemia and continues to be evaluated clinically in leukemias with NPM1 or KMT2A alterations, both as monotherapy and in combinations.

P=N/A, N=205, Not yet recruiting, Assistance Publique - Hôpitaux de Paris

P1, N=18, Recruiting, The First Affiliated Hospital of Soochow University | Trial completion date: Dec 2026 --> Jul 2027 | Initiation date: Nov 2025 --> Mar 2026 | Trial primary completion date: Jun 2026 --> Mar 2027

P1/2, N=447, Recruiting, Syndax Pharmaceuticals | N=67 --> 447

LCP remains a valuable therapeutic option for patients with HL in newly diagnosed AML. Our long-term experience supports its safety and efficacy, particularly in symptomatic patients, as a bridge to definitive therapy regardless of treatment intensity eligibility.

Our review underscores the need for genetic profiling to improve risk stratification and treatment. Given the limited documented cases, further research is essential to develop better therapeutic strategies for KMT2A-amplified B-ALL.

BCGitis in infants with acute leukemia is a rare complication that is likely associated with chemotherapy-induced immunodeficiency or immune reconstitution following chemotherapy, immunotherapy, or HSCT. While manifestations are typically localized, careful management is required to prevent further complications. This is particularly crucial for patients undergoing HSCT, where prophylactic antimycobacterial therapy may be considered in selected high-risk settings.

P2, N=70, Not yet recruiting, Uma Borate | Initiation date: Jan 2026 --> Apr 2026

P1, N=30, Recruiting, Andrew E. Place, MD | Active, not recruiting --> Recruiting | N=13 --> 30 | Trial completion date: Jul 2028 --> Jul 2030 | Trial primary completion date: Jul 2026 --> Jul 2028

This manuscript reviews the molecular rationale of menin inhibition for aberrant homeobox/myeloid ectopic insertion site 1 (HOX/MEIS1)-driven gene expression and leukemogenesis, clinical trial outcomes, and safety data for menin inhibitors, with a focus on recently FDA-approved revumenib and several other agents in development, ziftomenib (KO-539), bleximenib (JNJ-75276617), and icovamenib (BMF-219). We also focused our discussion on future directions to include resistance mechanisms, biomarker identification and monitoring strategies, and combination therapies. Menin inhibition is now being clinically integrated into relapsed/refractory and frontline treatment settings.