The CLL treatment paradigm has changed significantly over the past decade, with targeted therapies such as Bruton’s tyrosine kinase (BTK) inhibitors (BTKis) and BCL-2 inhibitors displacing chemotherapy-based treatments for most CLL patients. 

Monotherapy with the BTKi Imbruvica has been the preferred first-line therapy among physicians, inducing durable remissions in most patients. However, most of these remissions are only partial responses, and long-term treatment is required, which can be complicated by adverse toxic effects (cardiac arrhythmias, fungal infections, and bleeding) and the emergence of resistance. As such, Imbruvica’s long-standing supremacy in the first line is now under threat from newer, more tolerable, and more efficacious BTKis. In the US, Imbruvica is covered by Medicare as a Part D drug, and as such is set to see price reductions by 2026 under the Inflation Reduction Act.