apr-246 and Myelodysplastic-Syndromes

Targeting TP53 mutated myelodysplastic syndromes and acute myeloid leukemia remains a significant unmet need. Recently, new drugs have attempted to improve the outcomes of this poor molecular subgroup. The aim of this article is to review all the current knowledge using active agents including hypomethylating agents with venetoclax, eprenetapopt or magrolimab. We include comprehensive analysis of clinical trials to date evaluating these drugs in TP53 myeloid neoplasms as well as discuss future novel combinations for consideration. Additionally, further understanding of the unique clinicopathologic components of TP53 mutant myeloid neoplasms versus wild-type is critical to guide future study. Importantly, the clinical trajectory of patients is uniquely tied with the clonal burden of TP53, which enables serial TP53 variant allele frequency analysis to be a critical early biomarker in investigational studies. Together, significant optimism is now possible for improving outcomes in this patient population.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Biomarkers; Biomarkers, Tumor; Bridged Bicyclo Compounds, Heterocyclic; Clinical Trials as Topic; Humans; Leukemia, Myeloid, Acute; Mutation; Myelodysplastic Syndromes; Precision Medicine; Quinuclidines; Sulfonamides; Treatment Outcome; Tumor Suppressor Protein p53

This phase II study assessed the safety and efficacy of eprenetapopt in combination with AZA in untreated high or very high International Prognostic Scoring System-R. Fifty-two. In this very high-risk population of

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Humans; Leukemia, Myeloid, Acute; Middle Aged; Mutation; Myelodysplastic Syndromes; Quinuclidines; Tumor Suppressor Protein p53

Topics: Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Humans; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Quinuclidines; Treatment Outcome; Tumor Cells, Cultured

Topics: Azacitidine; Humans; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Quinuclidines; Tumor Suppressor Protein p53