Background In chronic lymphocytic leukemia (CLL), the association of genetic markers such as del(17p), TP53 and IGHV status with disease prognosis is well established. In clinical trials, treatment with Venetoclax in combination with Obinutzumab (VenO) has shown promising efficacy and good tolerability in all subgroups 1. However, there is limited real-world data in specific genetic subgroups. Aim Effectiveness and safety data were analyzed for therapy naive patients treated with VenO focusing on CLL patients with or without the genetic risk factors TP53 mut and/or del(17p) as well as IGHV status. Methods VeRVe is a non-interventional, observational, prospective study with 60 study sites in Germany, Austria, and Switzerland. CLL patients treated with VenO according to the local label 2 were included. Study documentation is possible at baseline, weekly during ramp-up, monthly until the end of month 6 and quarterly afterwards up to a maximum of 2 years. Response assessment was documented after ramp-up, 3, 12 and 24 months. Results Until April 12 th, 2023, 101 patients were enrolled and received at least one dose of Venetoclax, 42 % were IGHV unmutated. Baseline characteristics were balanced between the genetic risk groups. Patients with TP53 aberrations were older compared TP53 wildtype patients (71 vs. 66 a). 70% of patients with TP53 aberration, 68% of patients with wt TP53, 74% of patients with IGHVunmutated and 71% of patients with IGHVmut had at least 1 comorbidity. The best overall response rate after 12 months for 88 evaluable patients is shown in the figure. Estimated PFS-rate after 1 year was 93% in the total population, 100% in patients with TP53 aberrations, 91% in patients with wt TP53 95.1% of patients with IGHVunmutated and 82.5% of patients with IGHVmut. Estimated OS -rate after 1 year was identical to the estimated PFS. CTCAE grade AEs 3-5 were reported in 35% of the total population, in 21% in the TP53 aberrant, in 35% in the TP53 wt, in 33% in the IGHVunmutated and 10% in the IGHVmut population. A total of 3 patients had laboratory TLS. No new safety signals were detected. Conclusion In summary, both patients with or without TP53 aberration and with mutated or unmutated IGHV had high rates of best ORR, estimated PFS, and OS. Reassuringly, CR/CRi rates were high in patients with TP53 aberration or IGHV unmutated patients. Treatment was well tolerated. Disclosures DR has received honoraria or research grants from AbbVie, AstraZeneca, Gilead, Janssen, Verastem, Roche, Cellestia. IS has received honoraria from AbbVie, Amgen, AstraZeneca, BeiGene, Janssen, Roche, Servier. HH received speaker or consulting fees from AbbVie, AstraZeneca, Celgene, Janssen, Roche, and Beigene. CL received consulting fees from AbbVie, Amgen. TW received honaria or research funding from Novartis, Celgene, Roche, Bayer, Teva and Abbvie. CL and JH are employees of AbbVie and may own AbbVie stock. BS received speaker or consulting fees from AbbVie, Alexion, Amgen, AstraZeneca, BeiGene, BMS, Hexal, Janssen, Novartis, Pfizer, Sanofi-Aventis and SOBI. PP has received honoraria from Amgen, Gilead, Janssen, Sanofi-Aventis, Takeda. Honorarium paid by AbbVie was not related to authorship of this abstract. No honoraria or payments were made for authorship. AbbVie sponsored this study and contributed to the design, study conduct. AbbVie participated in the interpretation of data, review, and approval of the publication. All authors had access to all relevant data. Statistical support was provided by Daniela Giesder and Anna Eisen of GermanOncology GmbH, which was funded by AbbVie.