Dr Coombs on Switching to Treatment With a BCL-2 Inhibitor Vs a Covalent BTK Inhibitor in CLL/SLL

Catherine C. Coombs, MD, associate clinical professor, University of California, Irvine (UCI), UCI School of Medicine, discusses the feasibility of switching from treatment with a covalent BTK inhibitor to a BCL-2 inhibitor–based regimen vs a different covalent BTK inhibitor in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) treated in a real-world setting.

According to data presented at the 2023 International Workshop on CLL, patients who switched to a BCL-2 inhibitor–based regimen were more likely to respond to therapy and had a lower risk of disease progression and/or death compared with patients who received another covalent BTK inhibitor. Both groups exhibited very good response rates, Coombs explains, but investigators did notice a higher response rate among patients who transitioned to a venetoclax (Venetoclax)-based approach.

The patient group in this investigation was heterogeneous, Coombs continues. Notably, the selected approach was not kept to time-limited regimens, as many of these patients continued to use venetoclax as continuous monotherapy, Coombs explains. Treatments ranged from venetoclax alone to venetoclax in combination with rituximab (Rituxan), according to the schedule previously established in the phase 3 MURANO trial (NCT02005471), Coombs states, adding that some patients explored alternative schedules in the relapsed setting.

Although the response rates seen in this study favored the venetoclax-based regimen, they remained notably high for patients who switched from one covalent BTK inhibitor to another, she continues. Investigators also examined progression-free survival, which showed a trend favoring the venetoclax-based approach when unadjusted. This research further strengthens the evidence supporting venetoclax administration following treatment with a covalent BTK inhibitor.

Coombs notes that there are limited prospective data in this setting. The MURANO trial primarily included patients who were naive to BTK inhibitors but were heavily pretreated, Coombs states. Conversely, patients in the current investigation were less heavily pretreated, with approximately half of all patients in both treatment groups having received 1 prior line, Coombs concludes.