Dr Allan on the Importance of BTK Inhibitors and BCL2 Inhibitors in CLL

John N. Allan, MD, associate professor, clinical medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, discusses the importance of understanding fixed-duration treatment approaches with BTK inhibitors and BCL2 inhibitors in patients with chronic lymphocytic leukemia (CLL), highlighting data within this treatment armamentarium.

Allan begins by saying that, at the 41st Annual CFS®, he had the opportunity to present on the topic of fixed-duration treatment approaches for patients with CLL, specifically examining doublet and triplet combination strategies involving BTK inhibitors and BCL2 inhibitors. The conversation primarily revolved around providing updates, delving into the preclinical synergies observed between these agents, and the subsequent translation of these preclinical findings into clinical trials, Allan states. The central theme was understanding the expectations surrounding these drug combination approaches in CLL treatment, along with summarizing the reported outcome data to date, he explains.

Initially, fixed-duration treatment approaches involved doublet strategies such as venetoclax (Venclexta) plus rituximab (Rituxan), Allan expands. The phase 3 MURANO study (NCT02005471) evaluated this combination, comparing venetoclax/rituximab with bendamustine (Bendeka)/rituximab in patients with relapsed/refractory CLL, he says. At the 2023 EHA Congress, the 7-year data analysis update highlighted the ongoing progression-free survival benefit associated with venetoclax/rituximab, Allan emphasizes. Notably, patients also maintained an overall survival benefit with venetoclax/rituximab compared with bendamustine/rituximab.

Allan continues by saying that an interesting aspect of the study was the retreatment data, indicating that responses could be achieved, particularly in relapsed/refractory patients with brief remissions. However, this retreatment may not yield as profound or durable a remission as the first round of treatment, though the data to support this are limited and not entirely reflective of current patient treatment practices, he emphasizes. It remains uncertain how well this information translates to frontline patient treatment and retreatment. These nuances prompt contemplation on alternative treatment approaches such as continuous therapy with BTK inhibitors for patients with short remissions who have not been exposed to such treatments, Allan concludes.