Real-world study confirms efficacy of Venetoclax alone after BTKi treatment

Venetoclax-based therapy is an effective treatment option for patients with chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL) who are treatment-naïve or previously treated with a covalent Bruton tyrosine kinase inhibitor (cBTKi), according to a study. A multicenter, real-world analysis showed that venetoclax-based treatment after cBTKi was associated with durable remission. Veneclat has consistently shown efficacy and manageable side effects in patients with CLL/SLL, whether they are newly diagnosed or experiencing relapsed or refractory disease. However, there is limited evidence regarding the use of venetoclax in patients previously treated with a BTK inhibitor.

The CLL Collaborative Study of Real World Evidence (CORE) is a retrospective, international observational study involving 23 centers. The study focused on adult patients with confirmed CLL/SLL who received a venetoclax-based regimen after discontinuing a cBTKi-based regimen. Overall response rate (ORR) was calculated based on complete response (CR) or partial response (PR) among patients with documented response. Time to next treatment or death (TTNT-D) was measured from the date of initiation of venetoclax to change in treatment/death, whereas progression-free survival (PFS) was measured from the same date of disease progression/death.

Results are reported for the entire population and stratified by treatment regimen (first-line to second-line [1L→2L] and second- to third-line [2L→3L]) and whether 2L→3L received chemotherapy/chemoimmunotherapy before cBTKi. Among the 2020 patients included in CORE, 1287 (63.7%) received at least one cBTKi-based regimen. Among them, 184 patients (14.3%) discontinued cBTKi, of which 83 (45.1%) were intolerant and 78 (42.4%) had progression. These patients subsequently started venetoclat-based therapy, with 115 receiving venetoclat alone and 69 receiving venetoclat in combination with rituximab or obinutuzumab.

The average age when starting venetoclax was 68.6 years old, 69.0% of patients were male, and 31.0% had medical insurance. Unmutated IGHV was observed in 67.2% of patients tested, and 25.7% had 17p deletions or TP53 mutations. The average follow-up time from the start of treatment with venetoclax was 19.6 months. Among 127 patients (69.0%) with documented response, the ORR was 78.0% (CR, 43.3%; PR, 34.6%). The median TTNT-D in these patients was 39.5 months, with 12- and 18-month rates of 82.3% and 72.4%, respectively. The median PFS was 43.2 months, and the 12-month and 18-month PFS rates were 82.8% and 75.1%, respectively.

In 1L→2L patients (n=65) who initiated venetoclax-based therapy after cBTKi, the ORR was 84.1% (CR, 54.5%; PR, 29.5%). The median TTNT-D for these patients was "not reached," but the 12-month and 18-month rates were 85.0% and 73.9%, respectively. The median PFS was 43.2 months, and the 12-month and 18-month survival rates were 86.4% and 81.8%, respectively. Among 2L→3L patients (n=67) who initiated venetoclax-based therapy after cBTKi, the ORR was 78.3% (CR, 41.3%; PR, 37.0%). The median TTNT-D in these patients was 44.2 months, with 12- and 18-month rates of 83.1% and 76.5%, respectively. The median PFS of these patients was 44.1 months, and the 12-month and 18-month survival rates were 85.2% and 80.4%, respectively. Results for ORR, TTNT-D, and PFS were also similar in patients who did or did not receive chemotherapy or chemoimmunotherapy before cBTKi.

These clinical trial results are timely becauseCLL treatment modalities continue to evolve, providing multiple treatment options and providing clinicians with valuable evidence to inform modern clinical practice. As part of future work, this study will be further analyzed with a larger cohort and longer follow-up to add to the evidence in this regard.