P078 | A SIGNIFICANT DOSE REDUCTION OF VENETOCLAX DOES NOT AFFECT RESPONSE RATE AND OVERALL SURVIVAL OF AML PATIENTS NOT ELIGIBLE FOR INTENSIVE CHEMOTHERAPY

Background. The VIALE-A study showed that the combination of Azacitidine and Venetoclax (AzaVen) is effective in patients (pts) with Acute Myeloid Leukemia (AML) not eligible for intensive treatment. However, it is common experience that the original scheme of VIALE-A study is difficult to apply in current clinical practice, due to significant toxicity in elderly and frail pts, and needs for dose adjustments. Aim. The aim of the study is to retrospectively evaluate the outcome of pts, not eligible for intensive treatment, who received a first-line attenuated AzaVen scheme for AML. Methods. We retrospectively analysed data from consecutive pts with de novo or secondary AML treated with AzaVen at our centre from 2021 to 2025. Treatment responses were defined according to the 2022 AML ELN recommendations. Results. We included 18 consecutive pts (10 males, 8 females) diagnosed with AML (median age 80 years, range 62-92), treated with AzaVen; 39% of cases were secondary AML. Azacitidine was administered as per the original schedule. Venetoclax was administered at a dose of 100 mg per day in the first 10 days of the cycle, instead of the planned dosage of 400 mg for 28 days. Posaconazole prophylaxis was administered only at the end of the Venetoclax administration. Response was observed in 61% of pts, 44% of whom showed a complete response, with a median time to response of 1.9 months (range 0.3-4.2) and a median duration of response of 14.6 months (range 2.1-38.5). At a median follow-up of 9.0 months, the median overall survival (OS) was 13.2 months (range 1.3-42, Fig. 1A). Median OS was 23.7 months (range 1.3-42) in pts with de novo AML and 6.3 months (range 2.4-13.2) in pts with a secondary AML (p=0.0009) (Fig. 1B). Safety profile was favourable, since G3-4 neutropenia was 22% and febrile neutropenia 22%. Conclusions. Our attenuated AzaVen schedule has shown clinical results comparable to the VIALE-A study. In particular, the response rate was 61%, compared to 66% in VIALE-A and median OS was 13.2 vs 14.7 months, respectively. It should be noted that the median age in our study was 80 vs 76 years in VIALE-A. Safety profile was favourable. Despite the limitations of a small, retrospective, single-centre study, it can be hypothesized that a significant dose reduction of Venetoclax in this setting would not substantially affect treatment efficacy and, thus, overall survival, especially in pts with de novo AML, suggesting the need for further studies.