Dr Awan on Patient Characteristics Associated With CAR T-Cell Candidacy in CLL

“We are excited about the advent of noncovalent BTK inhibitors and BTK degraders. The field is moving forward nicely, and it’s great news for our patients.”

Farrukh Awan, MD, professor, Department of Internal Medicine, member, Division of Hematology and Oncology, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses how he determines CAR T-cell therapy and pirtobrutinib eligibility among patients with chronic lymphocytic leukemia (CLL).

Ideal candidates for CAR T-cell therapy in CLL are patients who have demonstrated refractoriness to both BTK inhibitors and BCL-2 inhibitors, Awan begins. The primary treatment challenge in this setting is that true refractory disease, as opposed to treatment intolerance, is often aggressive and difficult to control for extended periods, he says. This presents a critical need for effective bridging strategies to maintain disease control until CAR T-cell therapy can be administered, he notes.

Pirtobrutinib (Jaypirca) has emerged as a therapeutic option for patients with double-refractory CLL, providing several months of disease stabilization and serving as a potential bridge to CAR T-cell therapy, Awan emphasizes. Notably, this agent was granted accelerated approval by the FDA in 2023 for the treatment of adult patients with CLL or small lymphocytic lymphoma who received 2 or more prior lines of therapy, including a BCL-2 inhibitor and a BTK inhibitor. Further investigations should evaluate pirtobrutinib in combination with other agents to try to deepen remissions and improve disease control before proceeding with CAR T-cell therapy, he explains.

Additionally, the role of bispecific antibodies is evolving in CLL, with potential utility both as a bridging therapy prior to CAR T-cell therapy and as treatment following CAR T-cell therapy for patients with residual disease, according to Awan. As the CLL treatment paradigm continues to advance, novel approaches, such as other noncovalent BTK inhibitors and BTK degraders, are gaining traction.These emerging therapies represent new avenues for managing refractory disease, he concludes.