Outcome at Two Years after a Response-Adapted Approach with Azacitidine and Intensive Chemotherapy in Patients > 60 Years with Newly Diagnosed AML Treated within the DRKS00004519 Trial of the East German Study Group (OSHO)

Abstract The heterogeneity of AML requires a personalized treatment strategy to achieve a high initial response and translate this response into long-term survival. Based on a possible synergistic effect of azacitidine (AZA) and cytarabine (ARA-C) when AZA is given first through the induction of deoxycytidine kinase by AZA which phosphorylates ARA-C to its active compound, ara-CTP, priming with AZA was integrated with intensive chemotherapy (IC) in a response-based sequential approach in the multicenter RAS-AZIC (DRKS00004519) study for patients (pts) >60 years (y). The safety, the remission rate of 64%, and a low TRM of 10% up to day (d) 90 were previously reported (Jaekel et al, ASH 2017). The final results of outcome at two years are presented. Patients and methods: Pts >60 y with newly diagnosed AML (de novo, secondary, and therapy related) were included (n=109). All received priming with AZA (75 mg/m2/day s.c) for 7 days. Irrespective of baseline bone marrow (BM) blasts, pts with d15 blasts ≥45% received IC (Mitoxantrone 10 mg/m2/day d1-3 and ARA-C 1g/m2/BID d1,3,5,7). If the count was Results: Patient characteristics are shown in table 1. Median age was 70y. Treatment sequels were AZA1+AZA2, n=24 (22%); AZA1+AZA2+IC1, n=30 (27.5%); AZA1+ IC1, n=35 (32.1%); AZA1+ IC1+IC2, n=9 (8.3%)]. The median of days alive and out of hospital till d90 was 41 days. The centrally reviewed response rate was 64.2% [CR/CRi 57.8%; PR 6.4%]. Remissions were achieved with AZA therapy± only one cycle of IC in 91% of responders. Maintenance with AZA was started in 53/70 (76%) responders and 12 (17%) pts received allogeneic HCT. Response translated into an improved survival at two years with a median survival time of 22 months (m) vs 7m only in non-responders (p Conclusion: Integrating an epigenetic therapy with IC in elderly pts with AML in an individualized response-based approach is feasible with low TRM and yields responses at least comparable to those achieved with repeated cycles of IC across all cytogenetic risk groups even in pts >70y. Most importantly, response could be translated into an improved survival particularly in pts with favorable and int-I risk genetics. Relapse remains high in adverse genetics. The results might further be improved through mutational profiling which allows the integration of emerging targeted therapies. Disclosures Hanel: Roche: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Novartis: Honoraria. Sayer: RIEMSER Pharma GmbH: Honoraria. Niederwieser: Novartis: Research Funding; Miltenyi: Speakers Bureau. Al-Ali: Gilead: Consultancy, Research Funding; Otsuka: Consultancy, Honoraria; Alexion: Honoraria; Novartis: Consultancy, Honoraria, Other: Travel support, Research Funding; Celgene: Honoraria, Other: Travel support, Research Funding.