DP025 | INDUCTION THERAPY IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA: INNOVATIONS IN THE ERA OF HYPOMETHYLATING AGENTS AND VENETOCLAX COMBINATION THERAPY

Background Prior to the approval of hypomethylating agents (HMAs) in combination with venetoclax (Ven) as first-line therapy for newly diagnosed Acute Myeloid Leukemia (AML) in 2017, intensive chemotherapy (ICT) was the only viable option for achieving remission in fit elderly patients. However, little is known on how to choose HMA-Ven over ICT, balancing these patients’ fitness and ICT risks. This study aimed to evaluate the prognostic impact of HMA-Ven in elderly patients over 65 years of age with newly diagnosed AML, compared to ICT and HMA alone. Materials and Methods This is a multicentric retrospective study enrolling consecutive patients over 65 years with newly diagnosed AML between 2016 and 2021. Patients were categorized considering the cytogenetic and molecular European LeukemiaNet (ELN) 2017 classification in three groups: favorable, intermediate and adverse. Primary endpoint was 1-year overall survival (OS1) from diagnosis, according to the ELN 2017 classification and the first-line therapy chosen (ICT, HMAs, HMA-Ven and Best Supportive Therapy [BST]). Results We screened 476 patients. We excluded 142 patients not stratified according to ELN 2017 classification. The patients were divided into two groups: the first cohort included 193 patients from 2016 to 2018, of which 81 underwent to CT, 94 to HMA and 18 BST; the second cohort included 136 patients from 2019 to 2021, of which 52 underwent to CT, 48 to HMA, 30 to HMA-Ven and 6 BST. In 2016-2018 cohort, ICT achieved better outcomes in ELN 2017 favorable-to-intermediate risk patients compared to HMAs (Figure 1A, log rank=4.46, p=0.03). In the same cohort, no differences in terms of mortality were found comparing ICT to HMA in adverse risk patients (Figure 1B, log rank=0.96, p=0.32). In 2019-2021 cohort, patients with ELN 2017 adverse risk showed no significant differences in OS1 between ICT and HMA-Ven (Figure 1C, log rank=0.30, p=0.59), whereas both were superior to HMA alone (Figure 1C, respectively log rank=7.60, p=0.006 and log rank=4.65, p=0.031). Eventually, we observed that ICT in the 2019-2021 cohort had a significantly higher OS1 compared to 2016-2018 cohort (Figure 1D, log rank=6.23, p=0.01). Conclusion In ELN 2017 adverse risk, HMA-Ven provides a comparable outcome to ICT, avoiding the exposure of more vulnerable patients to the risks associated with ICT.