Emerging Developments for the Treatment of R/R CLL

Emerging Therapies and Future Directions in CLL Treatment

BTK degraders represent an exciting new therapeutic class that demonstrates activity after both covalent and non-covalent BTK inhibitor failure, addressing the important issue of acquired resistance mutations. These agents offer promise for overcoming resistance mechanisms that develop with continuous BTK inhibition. Bispecific antibodies, particularly acasunlimab, show encouraging clinical activity with achievement of MRD negativity, though optimal dosing schedules and cytokine release syndrome management protocols require further refinement. While promising, broad implementation awaits better understanding of safe administration practices. Next-generation BCL-2 inhibitors including lisaftoclax and sonrotoclax are in development, potentially offering advantages over venetoclax in terms of dosing convenience, monitoring requirements, or efficacy through different binding affinities for BCL-2 family proteins. The expanding therapeutic landscape provides hope for improved outcomes and treatment sequencing options for CLL patients across all disease stages.