1212 - Targeted agents in chronic lymphocytic leukemia (CLL): Data on outcomes and subsequent therapies of patients observed within the German CLL Study Group (GCLLSG) registry

Introduction: BCL2-inhibitors (BCL2i) and BTK-inhibitors (BTKi) have profoundly improved the outcome of patients (pts) with chronic lymphocytic leukemia (CLL) and are considered standard treatment. However, the translation from novel treatments evaluated within clinical trials into routine clinical practice can be complex. The German CLL Study Group Registry provides real world data of pts with CLL on therapy choices outside of clinical trials in Germany. We here present data on efficacy and subsequent therapies of a large cohort of pts treated with either BCL2i or BTKi.

Methods: Patients with confirmed diagnosis of CLL and with at least one documented first-line CLL treatment between July 1st 2014 and January 30th 2023 were included in this analysis. Treatments were categorized according to the backbone of therapy and pts were allocated to either the venetoclax or the BTKi cohort depending on their first treatment with targeted agents. Treatment sequences were visualized with a sankey-diagram. Time to next treatment (TTNT), event-free survival (EFS) and overall survival (OS) were analyzed using Kaplan-Meier methods.

Results: A total of 274 pts were treated with a venetoclax-based regimen while 915 pts were treated with a BTKi as first therapy using targeted agents. Median observation time from the first documented treatment in the venetoclax cohort was 26 months (range 0 – 296) and 78 months (range 0-266) for BTKi treatment.
For the venetoclax cohort, the median age at the time of first venetoclax treatment was 71 years (range 32 – 87) with 172 pts (62.8%) being male. Median CIRS score was 2 (range 0-13) and 12 pts (7.5%) had an ECOG performance status > 1. Among 57 pts with known molecular genetics, 32 pts (56.1%) had an unmutated IGHV status and 9 out of 51 evaluable pts (17.6%) had a deletion and/or mutation TP53 as high-risk feature. Applying the CLL-IPI, 11 out of 58 evaluable pts (19.0%) were in the very high-risk group.
In the BTKi treated cohort, median age at time of first BTKi treatment was 72 (range 32 - 92), with 628 pts (68.6%) being male. Median CIRS score was 3 (range 0-17) and 45 pts (9.5%) had an ECOG performance status > 1. Among 162 pts with available data, 108 pts (66.7%) had an unmutated IGHV status and 59 out of 130 evaluable pts (45.4%) had a deletion and/or mutation TP53. According to the CLL-IPI, 46 out of 145 evaluable pts (31.7%) were in the very high-risk group.
152 of 274 pts (55.5%) received venetoclax as firstline treatment (median prior treatments: 0, range 0-9) and 352 of 915 pts (38.5%) were treated with a BTKi in the first line (median prior number of treatments: 1; range 0-12).
Among all 222 administered treatments prior to venetoclax and 1090 treatments administered prior to BTKi, chemoimmunotherapy (70.3% and 68.3%, respectively) and chemotherapy (10.4% and 17.8%, respectively) were the most frequent. Following the first venetoclax or BTKi treatment, pts were mainly treated with targeted agent regimens. In the venetoclax cohort, 37 subsequent treatments were documented in 26 pts, 10 of the subsequent treatments (27.0%) were a venetoclax-containing regimen and 13 (35.1%) a BTKi-containing regimen. Within the BTKi-based cohort, 393 subsequent treatments were administered in 264 pts, 146 (37.2%) included venetoclax and 106 (27.0%) a BTKi.
Median EFS from the start of the first venetoclax treatment was 31.8 months, with a 2-year EFS rate of 66.6%. For the BTKi cohort, median EFS was 23.2 months, with a 2-year survival rate of 48.6%. Median TTNT was 63.7 months in the venetoclax cohort and 68.4 months for the BTKi cohort. Median OS was 96.5 months for the venetoclax cohort and 85.9 months for the BTKi cohort with a 2-year OS of 89.5% and 84.9%, respectively.

Conclusion: In our dataset of patients being treated within the GCLLSG registry between 2014 and 2023, targeted therapies with venetoclax were administered as firstline treatment in 152 of 274 pts (55.5%) while 352 of 915 pts (38.5%) were treated with a BTKi. If prior treatments were given, the majority of pts still received chemo(immuno)therapy. EFS, TTNT and OS were comparable between the venetoclax and BTKi-based treatment cohort.