Interim analysis after 3 months of AML patients treated with venetoclax + azacitidine – first effectiveness and safety data from the prospective real world vero study Free

INTRODUCTION

In Italy, the combination of Venetoclax+Azacitidine (Ven/Aza) is approved, as the standard of care, for the treatment of newly diagnosed acute myeloid leukemia (AML) adult patients (pts) ineligible for intensive chemotherapy. VERO (NCT06058741) is a prospective observational study designed to analyze treatment with Ven/Aza in a real-life settingin Italy.

METHODS

VERO study is currently ongoing in 25 clinical sites with 151 pts enrolled.This interim analysis reports data from Ven/Aza treatment for the first 3 cycles of the first 75 enrolled pts /151(Mar-Oct 2024).Mean age was 76.2 years old(yo)(±6): 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).This report presents preliminary effectiveness and safety data from 75 pts after 3 months of treatment, up to the cut-off date of Jan27^th2025(median follow-up of 110 days).Outcomes are reported using descriptive statistics.

RESULTS

Overall Response Rate (ORR) was 58.7% (44/75pts).The best OR achieved was composite Complete Remission (cCR:CR+CRi) in 38.5% with CR in 25.3%,CR with incomplete hematological recovery (CRi) in 8% and CR with partial hematological recovery (CRh) in 5.3%. A Morphologic Leukemia-Free State was achieved in 10.7% ,a Partial Remission in 5.3%, a Stable Disease in 13.3%, Progressive Disease (PD) in 4%. cCR rates at C1 were 21.5% and 13.9%, at C2 38.% and 12.0%, at C3 43.5% and 10.9%. cCR by molecular subgroups was: TP53m 50% (3/6 pts); IDH1/2m 57.1% (8/14 pts); FLT3m 54.5% (6/11pts);NPM1m 44.4% (4/11pts). cCR by age (<75yo 18pts ;75-80yo 31pts; >80yo 16pts) was 50%, 32.3%,37.5%, respectively. cCR in de novo AML (45pts) was 46.7% and in secondary AML (20pts) 20%. cCR in intermediate ELN22 risk category (13pts) was 61.5% and in adverse (36pts) 33.3%. cCR by ECOG 0/1 (47pts) was 42.6% and 20% for ECOG 2/3 (10pts).

The transfusion independence rate of pts at months 1,2,3 was 77.8%,42.6% and 58.8%, respectively.The median time to best response was 0.95 months (interquartile range: 0.7- 1.9). In our population 65 pts (86.7%), after C1, had at least one post-baseline response assessment.Measurable residual disease (MRD) evaluation was performed mainly by flow cytometry at C1 in 29 pts,at C2 in 13pts and at C3 in 7pts:negativity was achieved in 8pts (25.8%), 4pts (28.6%) and 3pts (30%), respectively.CR/MRD- in 12%; CRh/MRD- in 1.3%; CRi/MRD- in 1.3% .Three pts underwent bone marrow transplantation. An overall infection rate of 66.7% (any grade) on 57 evaluable pts was observed: bacterial 81.6%, viral 18.4% and fungal 5.3%.Cytopenia rate (any grade) was 51.7% (31/60 pts): febrile neutropenia 48.4%, neutropenia 51.6%, thrombocytopenia 3.2%.TEAEs incidence was 80%: infections/infestations were 45% including Aspergillus 1.7%, pneumonia 21.7%, sepsis 10%, septic shock 10%; cardiac disorders were 5%.Serious TEAEs incidence was 46.7%: infections/infestations were 54.3% including pneumonia 22.9%, sepsis 17.1%, septic shock 17.1%.Overall, study discontinuation due to TEAEs was reported in 26.7% (20pts), mostly due to infections (55%) and cytopenia (15%).The main causes of the 26 reported deaths were PD in 8pts, septic shock in 6pts.

CONCLUSIONS

Despite the short follow-up period and the limited sample size, these data highlight the treatment efficacy in different patient subgroups. Variations were observed based on molecular characteristics, age, pathological heterogeneity, and risk categories. Notably,CR rate increased as the cycles progressed, such as MRD negativity rate.cCR varied among molecular subgroups, showing higher rates in patients with FLT3m and IDH1/2m.Intermediate ELN22 risk pts showed a higher cCR rate than adverse risk pts. Median time to response was less than 1 month, indicating timely response assessment in real-life.

No new safety signals were reported.While cytopenia and infections were the most frequent AEs, impacting treatment discontinuation, the main death causes were PD and septic shock.

In conclusion, our data appear consistent with previously published results from both real-life setting and clinical trials^1-2, although they are only descriptive and no conclusions can be drawn from this interim analysis.