Pb1864: improved long-term survival of elderly adults with aml receiving intensive induction therapy followed by either allogeneic stem cell transplant or maintenance differentiative therapy

Topic: 4. Acute myeloid leukemia - Clinical Background: Long-term prognosis of acute myeloid leukaemia (AML) in patients above the age of 60 is still unsatisfactory, with 10-20% 5 year survival (Urbino I et al. Cancers 2021). New therapeutic approaches (particularly venetoclax + hypomethylating agents, CPX-351, gentuzumab ozogamicin + standard cytarabine/daunorubicine) look promising, however long term results are still lacking. Aims: We analyzed retrospectively our real life experience with a different approach on AML patients ≥ 60 year old, looking at the possibility to improve complete remission rate with age-adapted intensive chemotherapy and to prolong survival with either allogeneic stem cell transplant (SCT) or maintenance “differentiative” therapy, as previously described (Ferrero D et al. Ann Hematol. 2014). Methods: Here we report the outcome of 58 AML patients, with a median age of 67 (range 60-77) treated from January 2014 to June 2020. These patient, selected because of relative fitness to intensive treatments, represented 64% of all patients of the same age range with AML diagnosis at our Institution in the same years. The other 33 patients received hypomethylating agents only. According to ENL 2022 prognostic classification 13/58 patients were at “low risk”, 25 at “intermediate risk” and 17 at “high risk” because of unfavourable cytogenetic and/or secondary AML (8 with previous myelodysplastic syndrome, 6 with myeloproliferative neoplasm); 3 patients could not be prognostically evaluated because of cytogenetic analysis failure.2 patients were treated in late relapse after previous chemotherapy. All 58 patients received remission- aimed intensive chemotherapy (mainly FLAI regimen), with age and/or comorbidities-adapted dose adjustements. Post-remission treatment included 1-2 similar consolidation chemotherapy courses and remission monitoring by minimal residual disease (MRD) evaluation with immunophenotypic characterization + molecular analysis (when genetic marker available). 20 patients ≤70 year old with either poor/intermediate risk at diagnosis or MRD recurrence/ increment during CR received allogeneic stem cell transplant (SCT), whereas the other patients received a maintenance treatment with retinoids + dihydroxylated vitamin D3 + low dose 6-thioguanine/ cytarabine, as previously described. Results: Standard complete remission (CR) was obtained by 41 patients (most of them after 1 chemotherapy course), for a total rate of 70%, ranging from 92% among “low risk” to 47% among “high risk” patients. Four patients died in the first month from diagnosis for intracranial bleeding (2) or pulmonary infection (2). At a median follow-up of 63 months (range 29-98), 19 patients are alive, with a median overall survival (OS) of 22 months and 6 year OS of 33%. Median disease –free survival was 47 months (with 44% at 6 years from CR achievement). Among the 19 patients ≥ 70 year old, CR rate was 78% and median OS 10.5 months, with 4 patients still alive at 29, 33, 54 and 73 months, respectively, from diagnosis. Summary/Conclusion: In conclusion, in our real life experience, although with a not large casistics, 64% of our AML patients aged 60 to 77 (24% with secondary disease) could receive an intensive treatment with acceptable induction death and high CR rate. The combination of MRD monitoring, allogeneic SCT or “differentiative therapy” maintenance could allow a favourable long-term OS rate compared to those recently reported with new drugs. More extensive studies are of course needed to compare the different therapeutic strategies. Keywords: Elderly, Therapy, AML, Survival