Erba Explores myeloMATCH Substudies Targeting Genetic Diversity in AML, MDS

Harry Erba, MD, PhD, professor of medicine at Duke Cancer Institute, chair of the SWOG Leukemia Committee, and co-chair of the myeloMATCH Senior Science Council, discusses the specific substudies included in myeloMATCH, a trial representing a significant shift in how acute myeloid leukemia (AML) is treated by addressing the disease's complexity and genetic diversity.

Transcription:

0:09 | In order to improve outcomes for [patients] with acute myeloid leukemia and myelodysplastic syndromes [MDS], it is critical that we understand the heterogeneity of this patient population in terms of the drivers of the disease pathogenesis. We have a lot of information about the mutations that are present in patients with AML and MDS.

0:37 | Out of the 10s of 1000s of genes in each of our cells, there is only a handful, maybe 50 to 60, that are currently mutated in people with acute myeloid leukemia, and they fall into very distinct classes, such as splicing mutations, chromatin modifiers, DNA methylation, enzymes activating signals, transcription factors, cohesin molecules, and such. We truly believe that these mutations underlie a pathogenesis of the disease. We have already started to make great inroads into the treatment of acute myeloid leukemia by identifying some of these targets.

1:27 | Some of the targets identified are more common like FLT3, IDH1, [and] IDH2. Other mutations are now targets for other therapies, such as the Menin inhibitors and patients with NPM1 mutations and KMT2A. myeloMATCH attempts to identify these mutations at the time of diagnosis and then assign patients to clinical trials meant to optimize the initial therapy and then subsequent therapy for these patients based on this mutational analysis.

2:10 | myeloMATCH activated on May 16, 2024, and we already have patients accrued to the study. The idea here is that after a patient is screened and the genetic profile is defined, the patient will then be assigned to an appropriate study. Now, we plan to have studies for every subtype that we identified and plan to develop studies for new targets that are identified. But at this point, myeloMATCH is activating with 2 studies: 1 from the Canadian Cancer Trials Group in intermediate-risk AML as defined by [European LeukemiaNet (ELN)] 2017 criteria, and a SWOG study of high-risk, poor-risk, or average-risk karyotype AML as defined by ELN 2017.

3:16 | There are other studies coming. We are developing studies for NPM1, FLT3, for core binding factors, and those studies are coming for the initial treatment of younger patients with acute myeloid leukemia. We are doing a similar thing for older patients, identifying these mutations and then developing trials.