Clinical Outcomes of CLL Patients Treated with Venetoclax Under Real-World Conditions in Austria, Germany, and Switzerland after Treatment with Ibrutinib
Authors: Schwaner Ingo , Hebart Holger F. , Losem Christoph , Wolff Thomas , Lehmann Caroline , Huelsenbeck Johannes , Schmidt Burkhard , Pichler Petra , Rossi Davide 
Published: December 2024

Background
The BCL-2 inhibitor Venetoclax (V) is approved for the treatment of CLL as continuous monotherapy (VM) and in combination with the anti-CD20 antibody Rituximab (VR). The following prospective non-interventional observational study comprises different study arms for patients treated with VM and VR after treatment with Ibru.
Methods
Adult patients with CLL requiring therapy treated with V according to local label were included in this analysis. Patient 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. Analyses were performed for subgroups of VM and VR arm after treatment with Ibru.
Results
Until April 9, 2024, 86 patients after treatment with Ibru have been enrolled into the study (VM: 58, 67%; VR: 28, 33%). All included pts (100%) in both arms had received at least one dose of V (safety population). For 50 out of 58 patients in VM and 24 out of 28 patients in VR arm treatment response had been documented at least once (effectiveness population). Median age at baseline was 63,5 in the VM arm and 59 years in the VR arm, respectively. 79% of the pts in VM and 96% of pts. in VR arm had at least one comorbidity.
In both therapy arms, enrolled patients had a median of 3 (range 1-10) previous lines of therapy, including Ibru. In VM arm, 55% pts had previously been treated with R-Benda and 22% with FCR. In VR arm, 50% of the pts had R-Benda and 46% FCR. In the VM arm the median duration of prior Ibru therapy was 9 months (range 0.1 - 72 month). In the VR arm the median duration of prior Ibru therapy was 18 months (range 1 - 51 month). Most frequent reasons for discontinuation of Ibru therapy were AE/SAE (VM:23 pts, VR: 14 pts) and tumor progression (VM: 21 pts, VR: 10 pts).
Risk factors were nearly balanced in the VR arm (46% del(17p), 36% TP53 mutation and 43% unmutated IGHV) in comparison to the VM arm (34% del(17p), 36% TP53 mutation and 34% unmutated IGHV status).
The reported best overall response at 24 months after V initiation is 76 % (CR+CRi 42%; PR: 34%) for VM arm and 100% (CR+CRi 54%; PR: 46%) for VR arm (figure 1).
After a median follow-up of 23 months the estimated 24-months OS rate were 73.2% for VM and 76.6% in VR, whereas the estimated 24-months PFS rate was 62.4% for VM and 72.9% for VR, respectively.
67% of pts. in VM and 82% of pts. in VR arm had grade 3-4 AE. 4 pts died due to infection, progressive disease and poor general condition in VM and 2 pts died due to pneumonia and unknown cause in VR.
No new safety signals were observed.
Conclusion
In this analysis, enrolled patients in both groups had a median of 2 previous lines of therapy before starting Ibru. Before Ibr, the most pts in both groups had previously been treated with R-Benda or FCR. Although risk factors were nearly balanced VR and VM arm, the OS, PFS and ORR rates were higher in VR group than in VM group. In both groups, V treatment was well tolerated. V represents a suitable treatment option for heavily pretreated Ibru-exposed patients.