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Combination Therapy Shows Promise and Safety for Specific Genetic Types of Acute Myeloid Leukemia

Combination Therapy Shows Promise and Safety for Specific Genetic Types of Acute Myeloid Leukemia

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New clinical research indicates that combining standard AML treatment with targeted drugs like revumenib offers high remission rates and safety for patients with specific genetic mutations, paving the way for personalized therapy approaches.

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Recent clinical research has demonstrated that adding a new, recently approved drug to the existing standard treatment significantly improves outcomes for older adults newly diagnosed with acute myeloid leukemia (AML) featuring specific genetic alterations. This early-phase trial, conducted at UNC Lineberger Comprehensive Cancer Center and 11 other institutions nationwide, revealed high remission rates when combining the standard therapies azacitidine and venetoclax with the targeted drug revumenib.

The study focused on AML patients harboring two particular genetic mutations: nucleophosphmin-1 (NPM1m), which appears in about 30% of AML cases, and KMT2Ar rearrangements, present in roughly 5%. Both mutations are associated with specific gene expression profiles that drive leukemia progression. Targeted therapies, such as menin inhibitors like revumenib, have shown clinical activity especially in patients with these genetic features. Revumenib is an oral medication currently approved for relapsed AML with KMT2Ar mutations.

This trial utilized advanced genomic testing within a few days of blood collection to identify genetic alterations at diagnosis, allowing for personalized treatment strategies. The Phase I trial enrolled 43 patients aged over 60, who received a combination of standard chemotherapy and revumenib. The results were promising: an overall response rate of 88.4%, with 67.4% achieving complete remission. Remarkably, most responses occurred after just one or two treatment cycles, and within a year, nearly 63% of patients were still alive.

The findings have laid the groundwork for a larger Phase III trial to evaluate whether this combination therapy can improve overall survival. Dr. Joshua F. Zeidner, the lead researcher, emphasized that their results could transform treatment approaches for patients with these specific genetic forms of AML. The upcoming trial aims to include more centers to confirm these early encouraging results.

This innovative combination therapy underscores the importance of genetic profiling in AML management and highlights the potential for targeted treatments to improve prognosis, especially in older patients typically facing poorer outcomes.

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