SAFETY AND EFFECTIVENESS IN R/R CLL PATIENTS TREATED WITH VENETOCLAX IN COMBINATION WITH RITUXIMAB UNDER REAL‐WORLD CONDITIONS IN AUSTRIA, GERMANY, AND SWITZERLAND

Abstract

Introduction: In clinical trials, treatment of chronic lymphocytic leukemia (CLL) with venetoclax (Ven) has shown promising efficacy and good tolerability.1,2 However, patients treated in clinical trial are often not representative in daily practice. Prospective real-world data on Ven usage are limited. Objective: We conduct a prospective non-interventional observational study assessing effectiveness, safety, and quality of life in relapsed/refractory patients (RR) treated with Ven in Austria, Germany, and Switzerland. The population enrolled is representative for patients treated with Ven according to local label.3 This report focuses on patients treated with Ven in combination with rituximab (R). Methods: Adult patients with CLL requiring therapy treated with Ven+R according to local label are eligible for the study. Patient’s 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. Results: Until Nov 4th, 2022, 106 patients receiving VenR were enrolled, 105 with at least one dose of Ven (= safety population), for 87 treatment response had been documented at least once (= effectiveness population). Median age at therapy start was 74 years, 72.6% of patients were male, 76.4% had at least one comorbidity, most commonly cardiovascular (57.5%) and 73.6% received comedication. Patients were pre-treated with a median of 1 (range 1-10) line of therapy, e.g., chemo-immuno-therapy (CIT: 75.5%) or B-cell receptor inhibitors (34.9%). Del(17p), TP53 mutation, and presence of unmutated IGHV had been diagnosed in 23.6%, 24.5%, and 40.6%, respectively (excl. missing data: 28.7%, 30.6%, 69.4%). With a median observation time of 652 (range 14-1364) days, 93.3% of patients experienced at least one AE, 58.1% experienced CTCAE grade 3/4 AEs, SAEs were reported in 41.0%. Grade 5 AEs were reported in 10 patients, tumor lysis syndrome (TLS) in 12 patients (11.4%). The median for progression-free survival (PFS) and overall survival (OS) has not been reached, the 24-month estimates were 80.1% (PFS) and 84.1% (OS). The reported best overall response at 24 months was 88.5% (CR+CRi 59.8%; PR: 28.7%). Remissions continue to deepen with longer treatment duration. Conclusions: Under real-world conditions, VenR is used in elderly patients with comorbidities. The treatment was well tolerated. Most patients receive VenR in 2L of therapy after initial CIT. The response rate in patients presenting with high risk features, e.g., del(17p), TP53 mutation or unmutated IGHV, was high. Despite the advanced age of the enrolled patient population, PFS and OS estimates are comparable to pivotal phase III trial MURANO. The research was funded by: AbbVie sponsored this study and contributed to the design, study conduct. Keywords: molecular targeted therapies, ongoing trials Conflicts of interests pertinent to the abstract I. Schwaner Consultant or advisory role AbbVie, Amgen, AstraZeneca, BeiGene, Janssen, Roche, Servier. H. Hebart Consultant or advisory role AbbVie, AstraZeneca, BeiGene, Celgene, Janssen, and Roche C. Losem Consultant or advisory role AbbVie, Amgen T. Wolff Consultant or advisory role Novartis, Celgene, Roche, Bayer, Teva and Abbvie B. Schmidt Consultant or advisory role AbbVie, Incyte, Celgene, Novartis, Roche, Hexal, Biotest, Bristol-Myers Squibb, Daiichi-Sankyo, Janssen und Amgen D. Rossi Consultant or advisory role AbbVie, AstraZeneca, Gilead, Janssen, Verastem, Roche, Cellestia C. Lehmann Employment or leadership position: employees of AbbVie and may own AbbVie stock J. Benzel Employment or leadership position: employees of AbbVie and may own AbbVie stock J. Huelsenbeck Employment or leadership position: employees of AbbVie and may own AbbVie stock P. Pichler Consultant or advisory role Amgen, Gilead, Janssen, Sanofi-Aventis, Takeda