Dr Phillips on Evolving Treatment Strategies in Both MCL and CLL

Tycel Phillips, MD, hematologist-oncologist, associate professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses the evolution of treatment strategies for patients with either chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL), highlighting the differences between these hematologic cancers.

Phillips begins by stating that there are a variety of noteworthy drugs in the treatment paradigms for CLL and MCL. One such drug is pirtobrutinib (Jaypirca), a noncovalent BTK inhibitor, he says. Pirtobrutinib has demonstrated higher efficacy in patients with CLL compared with patients who have MCL due to the distinct mutational changes in the BTK gene between these diseases, Phillips explains. Furthermore, noncovalent BTK inhibitors, such as pirtobrutinib, can effectively overcome site mutations, making them highly effective in treating patients with CLL, he states.

Additionally, BTK degraders are emerging as significant players in treating patients with MCL, particularly those who have progressed despite using both covalent and noncovalent BTK inhibitors, Phillips continues. BTK degraders work by tagging BTK receptors for proteasome degradation, thereby eliminating the target altogether, rather than merely blocking signaling pathways, as previous treatments have done, he explains. Several companies are currently exploring the use of BTK degraders in MCL, promising a range of treatment options upon their regulatory approval, Phillips emphasizes.

These advancements, especially with BTK degraders and noncovalent BTK inhibitors, have also made a substantial impact in the treatment of patients with CLL, he expands. Although not curative, these drugs have significantly extended patient survival and improved the management of the disease, Phillips states. They enable a strategic shift from one drug to another, which can lead to what is termed a “functional cure,” where patients live with the disease rather than succumbing to it, he explains. This evolution in treatment strategies provides hope for better long-term outcomes for patients with CLL and MCL, Phillips concludes.