Real-World Effectiveness and Safety of Venetoclax in Combination with Obinutuzumab in Treatment-Naive CLL Patients - Data from the Observational Study Verve

Introduction

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. 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 treatment-naïve patients treated with VenO in Austria and Germany.

Methods

Adult patients with CLL requiring therapy 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 analysed descriptively and odds ratios were calculated by a logistic regression model.

Results

Until April 25th 2022, 70 VenO patients were enrolled, 64 received at least one dose of obinutuzumab and 61 of them also received at least one dose venetoclax. Median observation time was 7 months and for 46 patients, treatment response has been documented at least once. Median age was 66 years, 35% had a del(17p) and/or TP53 mutation (of 48 patients with available data) and 68% were IGHV unmutated (of 41 patients with available data). 57% had at least one comorbidity, most commonly cardiovascular (41%). Best overall response rate (ORR) within 12 months was 90% (43% CR/CRi and 47% PR) and 10% of patients had stable disease. No disease progression was documented so far. The median for progression-free survival (PFS) and overall survival (OS) has not been reached, the 12-month estimates were 96% (PFS and OS). Risk factors such as del(17p), TP53 mutation and IGHV status did not influence ORR with odds ratios (95% CI) of 1.1 (0.31, 2.72), 0.8 (0.26, 2.7) and 1.1 (0.36, 3.55), respectively. 49 patients (80%) had any AE, 23 patients (38%) a grade 3-4 AE and 8 patients (13%) experienced SAEs. Most common SAE (5 patients) was covid-19 infection. 2 Patients died due to covid-19 infections, during the ramp-up phase. No TLS occurred during Ven treatment.

Conclusion

Under real-world conditions, VenO treatment was well tolerated and led to high ORR and CR/CRi-rates in this population with high rates of high-risk features. With this short follow-up, estimated PFS and OS rates were very high. Overall, these real-world results confirm the favourable benefit-risk profile of VenO for treatment naïve CLL patients as observed in the pivotal CLL14 trial.

Schwaner:AbbVie: Honoraria; amgen: Honoraria; astrazeneca: Honoraria; beigene: Honoraria; celgene: Honoraria; janssen: Honoraria; novartis: Honoraria; roche: Honoraria; servier: Honoraria. Hebart:abbvie: Consultancy; astrazenece: Consultancy; bms: Consultancy; janssen: Consultancy; roche: Consultancy. Losem:abbvie: Consultancy; amgen: Consultancy. Wolff:abbvie: Honoraria, Research Funding; teva: Honoraria, Research Funding; bayer: Honoraria, Research Funding; roche: Honoraria, Research Funding; celgene: Honoraria, Research Funding; novartis: Honoraria, Research Funding; astrazeneca: Honoraria, Research Funding. Famulla:abbvie: Current Employment, Current holder of stock options in a privately-held company. Huelsenbeck:AbbVie: Current Employment, Current holder of stock options in a privately-held company. Schmidt:janssen: Consultancy; takeda: Consultancy; biotest: Consultancy; alexion: Consultancy; sanofi: Consultancy; novartis: Consultancy; incyte: Consultancy; abbvie: Consultancy. Pichler:sanofi: Honoraria; janssen: Honoraria; gilead: Honoraria; amgen: Honoraria; takeda: Honoraria. Rossi:Gilead: Other: honoraria, advisory board fees , Research Funding; AbbVie: Consultancy, Honoraria, Other: Travel Support, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel Support, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel Support, Research Funding; MSD: Other: advisory board fees ; BMS: Consultancy, Honoraria, Other: Travel Support; BeiGene: Consultancy, Honoraria, Other: Travel Support, Research Funding. Noesslinger:abbvie: Consultancy; beigene: Consultancy; celgene: Consultancy; roche: Consultancy; janssen: Consultancy; astrazeneca: Consultancy; gilead: Consultancy.