KMT2A rearrangement

Key advancements include the integration of FLT3 inhibitors into intensive chemotherapy and the emergence of venetoclax...Innovations such as the liposomal formulation CPX-351 and oral formulations of CC-486 and oral decitabine/cedazuridine have further optimized treatment delivery and improved patient quality of life...Current research is actively exploring next-generation inhibitors, antibody-drug conjugates, and cellular immunotherapies such as BiTEs and CAR-T cells. This review summarizes the recent pharmacological evolution in AML and discusses how these emerging therapies bring us closer to the ultimate goal of achieving a definitive cure.

P2/3, N=25, Recruiting, Medical University Of Lodz | Not yet recruiting --> Recruiting

We systematically synthesize recent clinical advances, from small-molecule inhibitors against protein-protein interactions (e.g., menin-KMT2A), to targeted degraders (PROTACs), epigenetic readers/writers inhibitors (e.g., BET, LSD1, DOT1L), and rational combination regimens with chemotherapy or immunotherapy. By integrating the biological characteristics of KMT2 with translational medicine and clinical evidence, this study provides a framework for advancing precision medicine approaches based on the molecular subtypes driven by KMT2.

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.