Real-world outcomes of newly diagnosed AML treated with venetoclax and azacitidine or low-dose cytarabine in the UK NHS

Venetoclax with azacitidine is the standard of care for patients with AML who are unfit for intensive chemotherapy, however uncertainties remain regarding the treatment schedule, accurate prognostication and outcomes for patients treated outside clinical trials. The option of venetoclax with low-dose cytarabine (LDAC) is also available, however it is not clear for which patients it may be a useful alternative. Here we report a large real-world cohort of 654 patients treated in 53 UK hospitals with either venetoclax and azacitidine (n=587) or LDAC (n=67). Median age was 73 and 59% had de novo AML. Most patients received 100mg of venetoclax with an azole antifungal. In cycle 1 patients spent a median of 14 days in hospital, 85% required red cell and 59% platelet transfusion and 63% required intravenous antibiotics. Supportive care requirements significantly reduced after the first cycle. Patients receiving venetoclax-azacitidine had a CR/CRi rate of 67%, day 30 and day 60 mortality of 5% and 8%, and median overall survival of 13.6 months. Mutations in NPM1, RUNX1, STAG2 and IDH2 were associated with improved survival, while age, secondary and therapy related AML, +8, MECOM rearrangements, complex karyotype, ASXL1 and KIT mutations were associated with poorer survival. Prognostic systems derived specifically for patients treated with venetoclax-azacitidine performed better than the ELN and MRC classifications, however improved risk classifications are still required. In the 149 patients with NPM1 mutated AML, outcomes were similar for those treated with venetoclax-azacitidine and venetoclax-LDAC.