Dr Khan on Key BTK Inhibitor Updates in Relapsed/Refractory CLL

“There’s a lot of work being done to see how we can further improve upon what we currently have, and what we can do when the patients progress on the current crop of BTK inhibitors. There are also more real-world analyses coming out investigating BTK inhibition and what happens afterward.”

Cyrus M. Khan, MD, an assistant professor of medicine at the Drexel University School of Medicine and assistant director of the Stem Cell Transplant Program at the Allegheny Health Network Cancer Institute, discussed the key updates from the 2025 ASCO Annual Meeting in BTK inhibitors for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL).

The main update presented at the 2025 ASCO Annual Meeting encompassed how to approach sequencing following the development of BTK mutations in CLL, Khan began. Available data with pirtobrutinib (Jaypirca), among other BTK inhibitors being developed, demonstrated that they could be effective in patients with BTK C481 and other mutations, he explained. Additionally, more research is currently underway to further identify sequencing strategies when patients experience disease progression on the currently available BTK inhibitors, he stated. Real-world analyses are also aiming to address gaps in investigating BTK inhibition and the approach following inhibition, he added. For example, determining how to use CAR T-cell therapy for the treatment of patients with CLL after disease progression on a BTK inhibitor and establishing whether BCL2 inhibitors work following progression on BTK inhibitors, he noted.

Furthermore, a notable abstract presented at the meeting was a real-world analysis on using CAR T-cell therapy in patients with CLL and other patients with B-cell malignancies who had disease progression on the currently available novel agents, Khan continued. Of note, the real-world analysis included data from 5 trials: the phase 1 TRANSCEND NHL 001 trial (NCT02631044), the phase 1/2 TRANSCEND CLL 004 (NCT03331198), the phase 3 TRANSFORM (NCT03575351), the phase 2 TRANSCEND PILOT 017006 (NCT03483103), and the phase 2 TRANSCEND FL trials (NCT04245839), including data from the CIMBTR registry. B-cell malignancies included in the analysis consisted of relapsed/refractory diffuse large B-cell lymphoma, follicular lymphoma, CLL, small lymphocytic lymphoma, and mantle cell lymphoma.