Treatment initiation pattern, ramp-up measures and management of AML patients treated in real life in Italy with venetoclax+azacitidine - first interim analysis of the prospective vero study

Abstract

Abstract Introduction The VERO study (NCT06058741)aims to collect real-world data on effectiveness and safety of the combination Venetoclax+Azacitidine (Ven/Aza) and to describe current treatment management of newly diagnosed AML patients who are ineligible to intensive chemotherapy (IC) in Italy. This analysis is focused on the treatment initiation pattern while demographics, effectiveness and safety are described in two different abstracts at the congress. Methods This Italian multi-center, prospective, observational study is ongoing in 25 hematological centers and was designed to enroll 150 patients. Key inclusion criteria: Adult patients with newly diagnosed primary or secondary AML, ineligible for IC; investigator's decision on patient treatment with Ven/Aza reached prior to and independently of recruitment into the study; treatment prescribed in accordance with the applicable approved label, local regulatory and reimbursement policies. This interim analysis was performed after 50% of the enrolled patients were followed-up for 3 months, at the cut-off date of 27Jan2025. Results This initial interim analysis reports data from Ven/Aza treatment for the first 3 cycles of the first 75 enrolled patients (Mar-Oct2024) /151. Mean age was 76.2 (±6) years old(yo): 24% of pts were >80 yo and 48% between 75-80yo. AML was categorized as de novo in 71% of pts, as secondary in 29%. NPM1 mutation was present in 16% of 69 tested pts , TP53 in 14% of 43 pts, IDH1/2 in 23% of 61 pts and FLT3 in 21% of 68 pts. The ELN22 risk classification was performed for 66 pts: the assigned risk was intermediate for 16 pts (21%), adverse for 41 (55%) (missing for 18 pts). In accordance with the guidelines1-2, a Tumor Lysis Syndrome (TLS) risk assessment was conducted prior to treatment with Ven during visit 1. Renal impairment was present in 10 patients (13.3%), with a grade of 1 to 3 observed in 7 patients (missing chronic kidney disease stage for 3 patients), while 65 patients (86.7%) did not present renal impairment. A hyperleukocytosis was observed in 17 patients (22.7%), while it was absent in 58 patients (77.3%). Prophylactic measures were adopted in 62 (82.7%) patients as follows, consisting of hypouricemic agents treatments in 42 patients, blood chemistry monitoring in 42 patients, cytoreduction in 26 patients, (24 treated with hydroxyurea and 2 with cytarabine) and intravenous hydration in 36 patients. The ramp-up was performed according to different schedules and as per label only in 11 patients: 100-200-400mg in 11 patients; 100-200mg in 20 patients; 50-100-200mg in 2 patients;10-20-50mg in 10 patients. Other treatment initiation schedules were observed in 8 patients. During cycle 1,Ven was administered to 74 patients, with a mediantreatment duration of 28 days (Q1-Q3: 21-28) per 28-day cycle and a median dose of 133.3 mg/day (100-225). In cycle 2, 53 pts received the treatment for a median of 28 days (Q1-Q3: 22-28) with a median dose of 100 mg/day (100-233).Finally, in cycle 3, 47 patients were treated for a median of 28 days (Q1-Q3: 21-28) with a median dose of 200 mg/day (100-400).Aza was used in combination with Ven, with a median dose of 75 mg for 7 days. Antifungal prophylaxis was administered to 51/75 patients (68%), mainly with posaconazole, for a median duration of 26 days.In addition, Ven median daily dose in patients treated with antifungal prophylaxis at cycle1 was 100 mg. G-CSF use was reported in 27 out of 47evaluable patients. Conclusions This interim analysis from the VERO study provides interesting insights into the real-world initiation patterns and management of Ven/Aza therapy for AML patients ineligible for IC in Italy.A diverse approach to dosing schedules,tailored to individual patient needs and baseline characteristics has been reported.Despite the presence of renal impairment and high tumor burden in a subset of patients, the TLS risk assessment was conducted properly and in accordance with guidelines1-2 for the administration of Ven/Aza.These initial results indicate that the treatment regimen is feasible for clinicians and patients, as demonstrated by the data on cycle duration.A variety of ramp-up dosages have been reported, probably due to specific patient's clinical conditions. These interim data are descriptive and no final conclusions can be drawn.Further data from a longer follow-up of the VERO study will provide more insights on effectiveness and safety of this combination therapy.