EHA highlights

In this video, Dr Adriano Salaroli, haematologist at the Institut Jules Bordet in Brussels, shares his congress highlights from EHA 2024.

For patients with chronic myeloid leukaemia (CML), the most interesting data at EHA 2024 came from the ASC4FIRST study, a randomized phase III trial comparing asciminib to all the current standard of care frontline BCR:ABL tyrosine kinase inhibitors (TKIs). At week 48, asciminib proved to be associated with a significantly higher rate of major molecular response (MMR) compared to the standard first line TKIs (67.7% vs. 49.0%; p< 0.001). Compared to the established TKIs, asciminib also came with a more favourable safety profile.¹

In the context of myelofibrosis (MF), EHA 2024 featured two interesting studies evaluating novel combination regimens with ruxolitinib. In the phase III MANIFEST-2 trial, combining ruxolitinib with pelabresib, an oral inhibitor of bromodomain and extraterminal proteins, resulted in a significantly higher percentage of JAK inhibitor naïve MF patients obtaining a spleen volume reduction of ≥35% (SVR35) compared to ruxolitinib alone (65.9% vs. 35.2% at week 24; p< 0.001). Furthermore, the addition of pelabresib to ruxolitinib also came with a trend for a lower symptom burden and improved anemia.² In a second phase III trial (TRANSFORM-1), adding the BCL2 inhibitor navitoclax to ruxolitinib resulted in a twofold increase in the percentage of JAK inhibitor naïve MF patients obtaining a SVR35 at week 24 (63% vs. 32%; p< 0.0001). Also in this trial, the combination therapy improved haemoglobin levels. Interestingly, the benefit obtained with navitoclax in this trial was particularly pronounced in patients with poor prognostic features.³

In the field of acute lymphoblastic leukaemia (ALL), Dr Salaroli discussed the results of a study evaluating the addition of blinatumomab to a paediatric-inspired prephase and consolidation treatment protocol (HOVON-146). The 4-year overall survival (OS) rate with the blinatumomab-containing regimen was reported at 86% in the cohorts of patients ≤40 years of age and in patients aged 40-60 years, while it was 50% in the subgroup of patients >60 years. This survival rate compares favourably to the OS rates observed in HOVON-100 evaluating a similar chemotherapy regimen without blinatumomab (4-year OS in patients ≤40 years: 76% [vs. 86%], >40 years: 51% [vs. 71%]).

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 72%, 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). Based on these results, Dr Salaroli beliefs that this almost chemotherapy-free ATRA-ATO regimen will become the new standard of care for patients with newly diagnosed, high-risk APL.