Highlights in acute myeloid leukaemia (AML)

In this video, Dr Fabio Andreozzi, haematologist at the Institut Jules Bordet in Brussels, discusses the key highlights from EHA 2024 in the field of acute myeloid leukaemia (AML)

Within the context of the BEAT AML Master Trial, investigators assessed the effect of adding the menin inhibitor revumenib to azacitidine + venetoclax in patients with KMTA2 rearranged or NPM1 mutated newly diagnosed AML who were ineligible for intensive chemotherapy. In the efficacy evaluable population (N=24) of this trial, the composite complete remission (CRc) rate was reported at 96%, with 92% of patients attaining minimal residual disease (MRD) negativity. Three patients proceeded to hematopoietic stem cell transplant (HSCT). Extended follow-up data were available for patients in the first cohort of this trial indicating a 12-month overall survival (OS) rate of 100%.¹

In a phase I/II study reported by Bataller et al., the safety and efficacy of decitabine/cedazuridine in combination with venetoclax and gilteritinib was evaluated in patients with FLT3-mutated, newly diagnosed, or relapsed/refractory (R/R) AML or myelodysplastic syndrome (MDS). Among newly diagnosed patients, an overall response rate (ORR) of 83% was reported while this was 44% in the R/R cohort. No dose-limiting toxicities were observed, although myelosuppression was frequent.²

Olutasidenib is a potent, selective, oral inhibitor of mutant IDH1. During EHA 2024, 5-year results were presented of a phase II study evaluating this agent in 153 patients with R/R IDH1-mutated AML. In this trial, an ORR of 48% was reported with a median duration of response of 15.5 months and a median OS of 11.6 months. Of note, this high rate of response was obtained in a patient population with a high percentage of intermediate or poor cytogenetic risk (90%) and 1-7 prior lines of therapy (median 2), including  venetoclax in 8% of patients.³

by Dr Andreozzi also selected two abstracts evaluating the integration of venetoclax in a high-intensity chemotherapy regimen. In the phase I/II SAL-RELAX trial, the combination of venetoclax with high-dose cytarabine and mitoxantrone resulted in a composite complete remission rate (CR and CR with incomplete blood count recovery) of 75% in a cohort of R/R AML patients. The safety profile of this regimen was acceptable.⁴ In a second study, the combination of intensive chemotherapy (FLAG-IDA) with venetoclax was evaluaeted in patients with newly diagnosed or R/R AML. This combination led to a complete response with complete blood count recovery (cCR) in 96% of newly diagnosed patients, with MRD-negativity in 88% of patients. After 30 months of follow, the median OS and event-free survival (EFS) were not reached (2 year rates 75% and 58%, respectively). In the R/R cohort, a cCR rate of 66% was observed, with MRD negativity in 76% of patients. The median OS and EFS in this patient group were 12 and 7 months, respectively. ⁵

During the plenary session of EHA 2024, Platzbecker and colleagues presented the first results of the APOLLO trial, a randomized phase III study evaluating the combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in patients with newly diagnosed, high-risk acute promyelocytic leukaemia (APL). Patients in the ATRA-ATO arm received two doses of idarubicin (12 mg/m² on days 1 and 3) and daily ATO (0.15 mg/kg) and ATRA (45 mg/m²) until a complete response was obtained. Subsequent consolidation therapy consisted of ATO (5 days/week, 4 weeks on 4 weeks off for 4 courses), in parallel with ATRA (2 weeks on 2 weeks off for 7 courses). Patients in the control arm received the AIDA regimen (i.e., ATRA + Idarubicin induction followed by chemotherapy-based consolidation [3 cycles] and maintenance therapy). After a median follow-up of 31 months, the ATRA-ATO regimen proved to be associated with a significantly better event-free survival (EFS) than the AIDA regimen, with 2-year EFS rates of 89% and 70%, respectively (p= 0.02). In addition, a trend for a better OS was seen with ATRA-ATO, with a 2-year OS rate of 93% as compared to 87% with AIDA (p= 0.33). ⁶