Second Line Treatment with Bruton Tyrosine Kinase Inhibitor (BTKi) or Bcl-2 Inhibitor (Bcl-2i) in Patients with Chronic Lymphocytic Leukemia (CLL): Primary Analysis of the Czech Study Group for CLL (CSCLL)

Introduction: Venetoclax in combination with rituximab (VenR) along with either ibrutinib or acalabrutinib monotherapy represent the most common regimens currently used for the treatment of relapsed/refractory (RR) chronic lymphocytic leukemia (CLL) in the Czech Republic. As all of these regimens are approved for identical indications in RR CLL, the selection of the most appropriate treatment depends on the drug toxicity profile and patient´s comorbidities. Methods: We conducted a retrospective analysis of data from the Czech National Registry of CLL patients (CLLEAR). Patients were treated in one of eight Czech hematological centres between December 2015 and June 2023. Only those who received chemoimmunotherapy in the first-line and Bruton tyrosine kinase inhibitor (BTKi) or Bcl-2 inhibitor (Bcl-2i) in the second-line treatment were included in the study. All patients fulfilled iwCLL diagnostic criteria and had provided informed consent before their data were captured in the CLLEAR. Key CLL-related clinical and laboratory parameters were obtained from the database (Table 1). Ibrutinib and acalabrutinib monotherapy were given at standard doses until disease progression (PD) or unacceptable toxicity. The combination of venetoclax and rituximab (VenR) was administered in the regular dosing schedule for 24 months. Results: Out of 291 patients included in the study, 70.1% (204/291) were treated with ibrutinib, 8.9% (26/291) received acalabrutinib and 20.9% (61/291) VenR. The median age at the start of the second-line treatment was 72.1 and 70.6 years, respectively (BTKi and Bcl-2i). There were no significant differences in sex, clinical stage, CIRS, creatinine clearance and time since diagnosis until the beginning of the second-line treatment. Bendamustine and rituximab followed by fludarabine, cyclophosphamide and rituximab were the most common regimens used in the firs-line treatment. Deletion (del) 17p and/or TP53 mutation, and del 11q were more frequent in the BTKi cohort, while unmutated IGVH gene was detected similarly in both groups (Table 1). Median follow-up was longer in BTKi than in Bcl-2i group (19.2 vs. 11.5 months). The overall response rate (ORR) was evaluated in 191 patients treated with BTKi and in 42 patients treated with Bcl-2i for at least six months. The ORR was comparable between the BTKi and Bcl-2i cohort, 90.6% (173/191) vs. 92.9% (39/42) (p = 0.774). More complete remissions (CR) were seen in Bcl-2i group, 12.0% (23/191) vs. 42.9% (18/