Dr Issa on Testing for NMP1 or KMT2A Alterations in AML

 was guideline-recommended for testing because it informs prognosis and may influence treatment decisions as far as transplant. 

[testing has become] more relevant with menin inhibitors, and knowing about the 

Ghayas C. Issa, MD, MS, a clinical and translational researcher in the Departments of Leukemia and Genomic Medicine at The University of Texas MD Anderson Cancer Center, discussed strategies for genetic testing in acute myeloid leukemia (AML), specifically focusing on 

Issa began by emphasizing the critical importance of these tests for informing prognosis and guiding treatment decisions. Regarding 

 mutations, guidelines have recommended testing for this alteration even prior to the development of menin inhibitors, Issa stated. Testing for 

 mutations can provide crucial prognostic information and can influence treatment decisions, such as the need for transplant, he added.

The standard approach for identifying this mutation is through next-generation sequencing (NGS), Issa noted. It is particularly important to retest for 

 at the time of relapse, as approximately 5% of cases may lose the 

 mutation, indicating that other mutations are driving the leukemia, Issa explained.

 alterations has become even more relevant with the emergence of menin inhibitors, Issa continued. Knowing a patient's 

 status provides important prognostic information and is now crucial for determining eligibility for menin inhibitors, he added. The most widely available test for identifying 

 rearrangement is fluorescence in situ hybridization (FISH), Issa said. Unlike 

 alterations are typically founding events, meaning they are likely to persist at relapse, he explained. However, there is a chance a 

 rearrangement might have been missed at diagnosis, especially if not immediately clear on baseline cytogenetics, Issa cautioned. Therefore, repeating FISH at relapse is important if it was not thoroughly conducted at diagnosis, Issa concluded.

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Ghayas C. Issa, MD, MS, discusses the optimal timing of and approaches to genetic testing for NPM1 and KMT2A alterations in AML.

Dr Issa on Testing for NPM1 or KMT2A Alterations in AML

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-rearranged leukemia, showing consistently the efficacy of revumenib, regardless of age…and this supports the label as a standard of care.”

Ghayas C. Issa, MD, assistant professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses key findings and clinical implications from the phase 2 AUGMENT-101 trial (NCT04065399) evaluating revumenib (Revuforj) in relapsed or refractory 

The AUGMENT-101 trial highlights the efficacy and safety of revumenib, a menin inhibitor, in patients with 

rearranged acute myeloid leukemia and acute lymphoblastic leukemia, Issa begins. This subset represents a high-risk population with limited treatment options, underscoring the importance of novel therapeutic agents, Issa explains.

 demonstrated consistent efficacy outcomes, supporting revumenib’s use as a standard of care treatment for patients with relapsed or refractory 

Specifically, revumenib achieved a complete remission (CR) or CR with partial hematologic recovery rate of 22.7%, with an overall response rate of 63.9%. These results were observed regardless of patient age, supporting the use of revumenib in both younger and older patients. Importantly, the durability of responses and minimal residual disease negativity observed in most responders further validate the drug’s clinical utility, he adds.

No new safety signals were reported, and no patients discontinued treatment due to cytopenias, differentiation syndrome, or QTc prolongation. Grade 3 or higher treatment-emergent or treatment-related adverse effects occurred in 91.4% and 54.3% of patients, respectively, of which 77.6% and 36.2% were serious.

The favorable safety and efficacy profile of revumenib positions it as a new standard of care for relapsed or refractory 

-rearranged leukemias, Issa concludes. This approval provides a new treatment option for patients with historically poor outcomes, addressing an unmet need in this population, Issa notes.

Ghayas C. Issa, MD, discusses the efficacy of revumenib in relapsed or refractory KMT2A-rearranged leukemias.

Ghayas C. Issa, MD

Articles

Dr Issa on Testing for NPM1 or KMT2A Alterations in AML

Dr Issa on the Efficacy and Safety of Revumenib in R/R KMT2A+ Leukemias