P060 | LOOKING FOR A WINNING STRATEGY FOR ACUTE MYELOID LUKEMIA PATIENTS REFRACTORY TO FIRST INDUCTION

Refractoriness of acute myeloid leukemias (AML) represent a difficult challenge for hematologists. At present, there are no defined strategies for the rescue of patients (pts) unresponsive to first induction. To evaluate the clinical characteristics of pts in this setting, as well as the biology of AML, the treatment received and their outcome, we carried out a retrospective study on AML pts refractory to first induction (ref) observed at the Hematology Division of ASST-Spedali Civili di Brescia. Between 2015 Jan, 1st and 2024 Dec, 31st 71 ref AML pts treated with curative intent were recorded. M/F ratio was 43/28 and median age 63y (range 21-75); a de novo AML diagnosis was reported in 46 (65%) pts. Only 3 pts were classified as favorable risk according to ELN 17 (NPM1-pos FLT3-ITDwt), whereas a complex karyotype was recorded in 27 (38%) pts. TP53 mutation, evaluated in 48 pts, was positive in 12 (25%). All but 3 pts, receiving hypomethylating agents (HMA) ± venetoclax (VEN), were treated with chemotherapy (CT) as 1st induction; 9 of whom received high dose cytarabine (HDAC). Sixty-four pts (90%) proceeded to 2nd line treatment with curative intent; non-intensive treatment (nIT) was chosen for 16 pts (13 HMA±VEN, 3 gilteritinib), the remaining 48 being treated with CT. Thirty of 64 pts (47%) achieved complete remission (CR). No differences in achieving CR after 2nd line were observed between nIT (7, 43%) and CT (23, 48%). One pt receiving HMA+VEN as 1st line was rescued with CT and none of pts receiving HDAC benefited from further CT. Overall, 32/71 (45%) underwent allotransplant (alloSCT), 26 (54%) after CT and 6 (37.5%) after niT (p=0.39). Five pts had active disease at alloSCT. After a median follow-up of 10.2 mo (range 0.2-100.4), 16/71 pts (22.5%) are alive, with a median overall survival (OS) of 12.5 mo. Median OS was significantly better in pts undergoing alloSCT (14 vs 5 mo, p=0.019), in those without TP53 mutation (11.4 vs 9 mo, p=0.016) and in pts receiving CT as 2nd induction (15.67 vs 11.33 mo, p=0.0326) (Figure 1). The prognosis of primary refractory AML remains poor regardless of salvage treatment type, particularly in p53 mutated pts. niT and CT showed similar efficacy as salvage therapy for achieving CR. CT as 2nd line treatment seems to be associated with better OS, at least in pts not treated with HDAC in 1st induction, although further studies with larger sample of pts are warranted to better define the most effective strategy.