1105 - SAFETY AND EFFECTIVENESS IN CLL PATIENTS TREATED WITH VENETOCLAX MONOTHERAPY IN AUSTRIA, GERMANY, AND SWITZERLAND - LONG TERM FOLLOW UP DATA

Background
In clinical trials, treatment of chronic lymphocytic leukemia (CLL) with venetoclax (Ven) has shown promising efficacy and good tolerability1. However, patients treated in clinical trials often represent a selected group and prospective real-world data are limited.

Aim
We conduct a prospective non-interventional observational study assessing effectiveness, safety, and quality of life in patients treated with Ven in Austria, Germany, and Switzerland. The population enrolled is representative for patients treated with Ven according to local label2. This report focuses on patients treated with Ven monotherapy.

Methods
Adult patients with CLL requiring therapy treated with Ven 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 2 years. Response assessment according to iwCLL criteria can be documented at the end of ramp-up, after 3, 12, and 24 months.

Results
The study started in November 2017. Until November 4th, 2022, 89 patients receiving Ven monotherapy were enrolled, 84 had received at least one dose of Ven (= safety population), and for 66 treatment response had been documented at least once (=effectiveness population). Median age at therapy start was 75 years, 59.6% of patients were male, 76.4% had at least one comorbidity, most commonly cardiovascular (56.2%), 67.4% received comedication. Patients were heavily pre-treated with a median of 2 (range 1-10) lines of therapy, i.e., chemoimmunotherapy (67.4%) and therapy with B-cell receptor inhibitors (66.3%). Del(17p), TP53 mutation, and presence of unmutated IGHV had been diagnosed in 43.8%, 40.4%, and 33.7%, respectively (excl. missing data: 49.4%, 48.6%, 63.8%). With a median observation time of 461 (range 1-1131) days, 91.7% of patients experienced at least one AE, 61.9% experienced CTCAE grade ≥3 AEs, SAEs were reported in 42.9%. Most common AEs were diarrhoea, thrombocytopenia, neutropenia (17.9%/16.7%/14.3%). 16 patients died. Tumour lysis syndrome (TLS) was reported in 9 patients (3 clinical TLS). This rather high rate may in part be due to advanced age of patients and/or incomplete laboratory monitoring, e.g., full laboratory values at 24 h post first dose of Ven were reported in only 49.4% of patients. Furthermore, only 72.6% of patients received hyperuricemic prophylaxis. Out of the 9 patients with reported or suspected TLS, 8 completed ramp-up, 1 patient discontinued the therapy.
The median for progression-free survival (PFS) and overall survival (OS) has not been reached, the 24-month estimates were 76.0% (PFS) and 75.7% (OS). The reported best overall response at 24 months was 80.3% (CR+CRi 42.4%; PR: 37,9%). Remissions appeared to deepen with longer treatment duration.

Conclusion
Under real-world conditions, Ven monotherapy is used in heavily pre-treated elderly patients. The treatment was well tolerated. TLS monitoring deviated from recommended lab monitoring procedures as specified in the Ven label. Despite the difficult-to-treat patient population, the response rate was high. Our study confirms findings from Ven Phase-II-studies in patients treated under real-world conditions.


References
1. Hallek and Al-Sawaf, Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures, Am J Hematol. 2021 Dec 1;96(12):1679-1705
2. Venetoclax SmPC, March 2022