Pb1938: real world effectiveness and safety of venetoclax in combination with obinutuzumab in treatment naive cll patients – data from the observational study verve

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: In the CLL14 trial, treatment of first line chronic lymphocytic leukaemia (CLL) with a combination therapy of venetoclax and obinutuzumab (VenO) has shown promising efficacy and good tolerability (Al-Sawaf et al., Lancet Oncol. 2020;21(9):1188-1200). However, prospective real-world data on VenO are limited. Aims: In the prospective non-interventional observational study VeRVe we assess effectiveness, safety, and quality of life in patients treated with Ven regimens in Austria, Germany, and Switzerland. This report focuses on therapy naive patients treated with VenO. Methods: Adult patients with CLL requiring therapy and treated with Ven according to local label are eligible for the study. Patients’ visits are scheduled at the physician’s discretion and according to clinical practice. Study documentation is possible at baseline, weekly during ramp-up, monthly until the end of 6 months and 3-monthly afterwards up to a maximum of 3 years. Response assessment according to iwCLL criteria can be documented at the end of ramp-up, after 3, 12, and 24 months. Data was descriptively analyzed and odds ratios were calculated by a logistic regression model. Results: Until November 3rd, 2022, 93 VenO patients were enrolled, 86 received at least one dose of obinutuzumab and 82 of them also received at least one dose venetoclax. Median observation time was 9.5 months and for 67 patients, treatment response has been documented at least once. Median age at the timepoint of diagnosis was 61.5 years, 22% had a del(17p) and/or TP53 mutation (of 61 patients with available data) and 63,8% were IGHV unmutated (of 62 patients with available data). 73.1% had at least one comorbidity, most commonly cardiovascular (40.9%). Best overall response rate (ORR) within 12 months was 91% (49% CR/CRi and 42% PR) and 9% of patients had stable disease. No disease progression was documented so far. The median progression-free survival (PFS) and overall survival (OS) has not been reached, the 12-month estimates were 95.8% (both PFS and OS). 68 patients (82.9%) had any AE, 28 patients (34.1%) a grade 3-4 AE and 16 patients (20%) experienced SAEs. Most common SAE (7 patients) was covid-19 infection. 6 patients died, 3 of them died due to covid-19 infections, during the ramp-up phase. TLS was diagnosed for one patient during Ven treatment. Summary/Conclusion: Under real-world conditions, VenO treatment was well tolerated and led to high ORR and CR/CRi-rates in this population. With this short follow-up, high PFS and OS rates were estimated. Overall, these real-world results confirm the favourable benefit-risk profile of VenO for treatment naive CLL patients as observed in the pivotal CLL14 trial. Figure 1: Best ORR after 12 monthsKeywords: Venetoclax, Chronic lymphocytic leukemia