P071 | ASSOCIATION OF GLASDEGIB + LOW-DOSE CYTARABINE IN THE REAL-LIFE TREATMENT OF VERY FRAIL ELDERLY PATIENTS WITH ACUTE MYELOID LEUKEMIA

Survival of very frail/elderly patients (pts) with Acute Myeloid Leukemia (AML) not eligible for standard induction chemotherapy is very poor. Recently, the association of glasdegib + low-dose cytarabine (AraC) was registered for these pts, but real world data are still limited. In this real-life analysis, data from 32 very frail pts with AML treated upfront with glasdegib + AraC in 10 Hematologic Centres in Italy were retrospectively collected and analysed. Composite overall response rate [ORR; complete remission (CR) + CR with incomplete hematologic recovery (iCR) + partial remission (PR)], duration of response, overall survival (OS) and safety were assessed. Patient characteristics at AML diagnosis are reported in the Table 1. Of note, among 30 pts with an evaluable cytogenetic, 11 (36.7%) had a complex karyotype. Eight pts had available NGS data: the most commonly mutated genes were IDH1 (3 cases), RUNX1 (3 cases) and ASXL1, SRSF2, P53 (2 cases each). AraC was administered subcutaneously for 10 days/month [20 mg twice a day in 17 pts (53.1%) and 40 mg once a day in 15 pts (46.9%)] while glasdegib was given orally 100 mg/day. Pts were treated for a median of 2 courses (IQR 1 – 3). As to toxicity, 21 pts (65.6%) had at least one hematologic toxicity of grade 3-4 and severe neutropenia (PMN < 0.5 x 109/L) was reported in 15 pts (46.8%). Sixteen pts (50.0%) had at least one infective episode during treatment: pulmonary infections were reported in 7 pts (21.8%). Among 30 pts evaluable for response 3 achieved CR/iCR and 4 PR, with an ORR of 23.3% and a median response duration of 2.0 months (95%CI 0.9-4.1). At the last observation, 24 pts (75.0%) had died, 6 (18.7%) were alive and 2 (6.3%) were lost to follow-up. Median OS from AML evolution of the whole cohort was 3.3 months (95%CI 1.6 - 5.0). Pts with any type of response had a significantly longer OS compared to pts with progressive/stable disease [median 15.6 months (95%CI 2.5 – 34.0 versus 2.5 (95%CI 1.0 – 4.1) months, respectively (p=0.016)]. Our real-life data suggest that glasdegib + AraC combination may benefit a subset of very frail/elderly AML pts, allowing an ORR of about 20% in subjects otherwise unfit for curative therapies. In addition, the potential OS advantage observed in responding pts highlights the need for a better selection of pts candidates to this association. Moreover, the addition of NGS- driven targeted therapies should also be explored in the near future in this subset.