Highlights in Acute Myeloid leukaemia (AML)

While ASH 2024 did not feature any major, practice changing studies in the field of acute myeloid leukaemia (AML), Dr Koen Theunissen, heamatologist at the Jessa Hospital in Hasselt (Belgium), did find some interesting presentations that are building further on the advancements of the last decade.

One of the major breakthroughs for patients with AML consists of the combination of a hypomethylating agent (HMA) and venetoclax as a frontline treatment for AML patients who are ineligible for intensive induction therapy. Despite the potency of this regimen, certain patient populations, such as patients with a TP53 mutation, or patients with a mutation in the RAS pathway or FLT3, continue to have a more dismal prognosis. To address this medical need, several studies are currently looking into the effect of adding a third agent to this HMA-venetoclax backbone.

A first of these studies presented at ASH 2024 retrospectively evaluated the addition of a FLT3 inhibitor (gilteritinib, quizartinib, sorafenib or midostaurin) to HMA-venetoclax in a cohort of 73 patients with newly diagnosed, FLT3-mutated AML.1 Interestingly, these triplet combinations led to very high response rates, with a composite complete response rate (CRc) of 93% and 81% of responders with adequate samples obtaining minimal residual disease (MRD) negativity. The median overall survival (OS) among patients with a FLT3 internal tandem duplication (ITD) mutation was reported at 28.1 months, which is more than twice as long as the 9.9-month median OS seen in the pivotal VIALE trial.1

A second abstract described the results of a phase Ib/II study evaluating the combination of the IDH1 inhibitor ivosidenib with venetoclax with or without azacitidine in a cohort of 56 patients with an IDH1 mutant neoplasms. Of the patients included in the study, 70% had a newly diagnosed AML, while the remaining 30% was made up of patients with relapsed-refractory AML, a myelodysplastic syndrome (MDS), or a myeloproliferative neoplasm (MPN). Among the newly diagnosed AML patients, a very promising CRc rate of 94% was reported. Across the entire study population, the 3-year OS rate reached 71%, comparing very favorably to the results obtained in the AGILE and VIALE studies.2 

A third and final presentation that was selected by Dr Theunissen discussed the results of a retrospective COMMAND study looking into the impact of time from diagnosis to treatment (TDT) on the outcome in adult AML patients treated with an HMA-venetoclax combination.3 Interestingly, this analysis revealed that a longer TDT was associated with a better OS. This benefit was seen irrespective of the presence of dismal prognostic factors, ECOG performance status, age and disease burden.3 While these data suggest that postponing the treatment in these patients does not lead to a worse outcome, one must note that the analysis only included patients who received therapy. As such, patients who never made it to the treatment were excluded from the analysis. Nevertheless, these data provide reassurance on the fact that physicians can wait for the results of the molecular profiling analysis in adult AML patients before starting therapy. Furthermore, the 2-3 weeks that it takes to obtain this result can be used for ‘prehabilitation’. In fact, a poor performance status is an independent predictor for a worse outcome in AML. Whenever possible, it is therefore worthwhile to invest in improving the performance status of AML patients prior to the start of therapy.