Dr Danilov on the Importance of Using BTK as a Target in CLL Treatment

Alexey Danilov, MD, PhD, hematologist-oncologist, associate director, Toni Stephenson Lymphoma Center, professor, Division of Leukemia, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, discusses the importance of using BTK as a target in the management of chronic lymphocytic leukemia (CLL), as well as recent updates on BTK degraders within the CLL treatment paradigm.

BTK has been well established as a crucial target in the treatment of patients with B-cell non-Hodgkin lymphoma (NHL) and CLL through both preclinical and clinical research, Danilov begins. BTK inhibitors have significantly transformed the management of various lymphomas and CLL, with 2 classes of drugs currently approved: covalent and noncovalent BTK inhibitors, he explains. Recent data on pirtobrutinib (Jaypirca), a noncovalent BTK inhibitor approved for patients with CLL and mantle cell lymphoma (MCL) who are refractory to multiple agents, have shown impressive efficacy and good safety profiles with this agent, Danilov reports.

Additionally, a new class of proteolysis-targeting chimeras, specifically BTK degraders, has emerged, and data have shown promising results with these agents, he continues. At the 2024 EHA Congress, data on NX-5948, a novel BTK degrader, demonstrated effectiveness in patients with BTK inhibitor–resistant CLL, Danilov adds.

Regarding recent updates and data on BTK degraders, the space has had particularly noteworthy updates, he expands. At the 2024 EHA Congress, studies on BGB-16673 and NX-5948 reported impressive response rates of approximately 70% in patients with BTK inhibitor–refractory CLL, Danilov elucidates. These studies also highlighted the safety of these agents, showing BTK-inhibitor–like adverse effects with few high-grade toxicities, according to Danilov. Although longer follow-up is needed to determine the duration of response with these agents, the initial efficacy data are promising and have already been life-changing for some patients, Danilov imparts.

Importantly, BTK degraders are effective regardless of the specific BTK mutation present, including in pirtobrutinib-resistant disease, he notes. This mechanism of action highlights BTK degraders as a crucial and effective emerging class of agents in the treatment of patients with CLL and NHL, Danilov concludes.