In this study that was presented by Uma Borate we analysed our Beat AML dataset for patients with MPM1 and KMT2A rearrangements, both who respond well to menin inhibitors. Both of these mutations occur more frequently in younger AML patients and so the study was done to be able to characterise the survival and outcomes of these patients in the overall population of newly diagnosed AML patients 60 years and older.

The primary endpoint of this retrospective analysis was to determine the prevalence and outcomes of these mutations in newly diagnosed AML patients 60 years and older with the therapies that were available during this dataset collection which was from November 2016 to June 2024.

The results of this analysis show that 18.9% of the patients enrolled into the Beat AML master trial had an MPM1 mutation and that we had 3.6% of the patients had a KMT2A rearrangement. We saw that the MPM1 mutated patients had a median overall survival of 18.4 months which included all therapies. However, when we separated out the therapies that the patients received we saw that the median overall survival was 21 months for patients who received treatment on the Beat AML master study which was 35% of the patients in this analysis. We saw that 19% of the patients in this analysis that received venetoclax and azacitidine or a hypermethylating agent off treatment had a median overall survival of 22 months, which is comparable.

We also saw that 28% of the patients in this cohort received intensive chemotherapy with a median overall survival of 41.6 months and that 8% of the patients received non-intensive treatment with a median overall survival of 6.3 months.

For the KMT2A patients we saw that 23 of these patients had treatment-related AML and that 31% of these patients had complex karyotype. The median overall survival of these patients, regardless of treatment, was 6.5 months. When we broke this down by the treatments that they received, we saw that 38% of the patients received a treatment on the Beat AML study with a median overall survival of 31.6 months. We saw 15% of the patients received venetoclax and a hypermethylating agent with a median overall survival of 5 months. With the 15% of patients that received intensive chemotherapy they had a median overall survival of 12.7 months. Then there was 15% of the patients that received non-intensive chemotherapy and they had a median overall survival of 2.9 months.

The clinical significance of these results come from the study is that this is one of the largest cohorts of KMT2A rearrangement in older patients that has been analysed to date. We see that the targeted approach for KMT2A patients had a great increase on the median overall survival of 31.6 months when compared to intensive chemotherapy of 12.6 months. If these patients aren’t candidates for intensive chemotherapy that drops to 5 months with venetoclax and hypermethylating agents. So therefore it is really important for patients to get these targeted treatments and we’re really looking forward for FDA approval of [??] for KMT2A in the newly diagnosed setting as they have recently been approved for relapsed/refractory patients.

For the future of this study we will do another data refresh. We do have a partnership with Syndax Pharmaceuticals where KMT2A and MPM1 patients are being treated in the newly diagnosed setting. So we should be able to have this data up front with revumenib/ venetoclax/azacitidine to see how that also increases median overall survival for these KMT2A patients and we’ll be looking for that in the future.