Advances in Risk Stratification and Treatment for Patients With AML

At the 2024 Lymphoma, Leukemia & Myeloma (LL&M) Congress in New York, New York, Jonathan Canaani, MD, Weill Cornell Medicine, New York, New York, discusses advancements in risk stratification and prognosis among patients with acute myeloid leukemia (AML), while highlighting the ongoing challenge of managing TP53-mutated disease.

“Over the past 2 to 3 years, we're seeing more sophisticated risk certification, both for intensively treated AML patients and non-intensively treated AML patients based on just a 3 or 4 gene classifier. Hopefully, with the introduction of novel therapeutics such as menin inhibitors, our patients will fare better,” concluded Dr Canaani.

Transcript:

I'm Jonathan Canaani. I'm from Weill Cornell Medicine from the NYP Brooklyn Methodist Hospital. I gave this talk at the LL&M 2024 meeting [regarding] updates in AML diagnosis and risk stratification.

Over the past 5 to 10 years, we've seen nice strides going forward, both in AML prognosis and risk stratification. Outcomes are still suboptimal, but they are improving slowly. We have new therapies coming in. Supportive care is better, early diagnosis as well. Over the past years, fit patients are treated with intensive chemotherapy [and are] risk-stratified nowadays, according to the European Leukemia Network (ELN) 2022 risk stratification model.

This risk stratification model is applicable only to patients who get intensive chemo[therapy] treatment. We know from recent studies basically published last year, both from the PETHEMA Spanish Leukemia group and from the Chemotherapy Committee of Cancer and Leukemia Group B (CALGB), that patients with favorable risk ELN reach 3-to-5-year overall survival rates of nearly 70%. Those with intermediate risk, probably around 50%. Unfortunately, patients with poor-risk ELN only reached a 30% 3-year overall survival mark.

Adding new therapies such as BCL-2 inhibition with venetoclax to the cladribine, cytarabine, idarubicin (CLIA) regimen or to the fludarabine, cytarabine, idarubicin, G-CSF (FLAG-Ida) regimen seem to be improving the outcomes. We're also adding newer FMS-like tyrosine kinase 3 (FLT3) inhibitors, to FLT3 mutated patients; quizartinib and most likely gilteritinib will also be added, possibly also IDH1 and 2 inhibitors will be added to intensive chemotherapy.

What we've learned recently is that from UK and CRI data is that nowadays we can specifically risk-stratify NPM1-mutated AML. We know this is a favorable risk disease, but we know that 50% of patients will eventually relapse. Their data indicate, [which was] just recently published in Blood, is that if you look also in addition to NPM-1, FLT3-ITD, [ ], and Wilms tumor [gene] 1 [(WT1)], if patients with NPM-1 harbor 2 or 3 of these mutations, they do worse.

This possibly identifies a high-risk group which might benefit from additional novel therapies [regarding] patients who are receiving low intensity therapies such as basically a hypomethylating agents (HMA) azacitidine or decitabine in addition to venetoclax-based therapy.

Just published data in Blood in 2024 shows that if you look specifically at 4 genes: TP-53, FLT3-TD, NRAS, and KRAS, you can risk stratify patients. Patients who are not mutated for any of these genes have higher benefit. Their median overall survival is over 2 years. Patients who are mutated for either FLT3-ITD, NRAS or KRAS, but are TP53 wild type have, I would say, intermediate prognosis with a median overall survival of 12 months. Whereas patients, [with] TP53 mutations don't do well with current therapies.

This is definitely an unmet medical need. Over the past 2 to 3 years, we're seeing more sophisticated risk certification, both for intensively treated AML patients and non-intensively treated AML patients based on just a 3 or 4 gene classifier. Hopefully, with the introduction of novel therapeutics such as menin inhibitors, our patients will fare better. Thank you so much.

Source:

Canaani J. Updates in AML Diagnosis and Risk Stratification. Presented at Lymphoma, Leukemia & Myeloma Congress; October 16-19, 2024. New York, NY.