Dr Dorritie on the Use of Pirtobrutinib Following Prior BTK Inhibition in CLL

“[Liso-cel] is a newer option for patients…. It is important to get the word out to community [oncologists] that patients do better with CAR T-cell therapy and that they should be referred to tertiary centers."

Kathleen A. Dorritie, MD, a hematologist/medical oncologist at the University of Pittsburgh Medical Center Hillman Cancer Center, discussed data that inform the current treatment paradigm of BTK inhibitors and CAR T-cell therapy for the treatment of patients with chronic lymphocytic leukemia (CLL).

Prior data have demonstrated the activity of pirtobrutinib (Jaypirca)—the first and only noncovalent, reversible BTK inhibitor—in patients with CLL who previously developed resistance to covalent BTK inhibitors, such as acalabrutinib (Calquence), ibrutinib (Imbruvica), or zanubrutinib (Brukinsa), Dorritie began. Findings from the phase 1/2 BRUIN trial (NCT03740529) established pirtobrutinib as an important therapeutic option in this setting, she explained.

Additionally, at the 2025 ASCO Annual Meeting, updated data were presented regarding the efficacy of lisocabtagene maraleucel (liso-cel; Breyanzi) in patients with CLL. Notably, in ​2024, the FDA approved liso-cel for the treatment of adult patients with relapsed or refractory CLL or small lymphocytic lymphoma who have received 2 or more prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. Importantly, real-world outcomes with liso-cel were shared at ASCO 2025, providing evidence to support the use of this agent beyond the clinical trial setting, according to Dorritie. In these analyses, liso-cel was compared with standard-of-care (SOC) chemoimmunotherapy regimens. Both progression-free survival and overall survival were superior in the liso-cel cohort relative to the SOC cohort, reinforcing the clinical benefit of CAR T-cell therapy in CLL, she said.

These real-world findings underscore the growing role of CAR T-cell therapy as a viable and effective treatment modality in CLL, Dorritie emphasized. They further highlight the importance of raising awareness among community oncologists regarding timely referral of eligible patients to tertiary centers where cellular therapy can be delivered, as patient outcomes are demonstrably improved with this approach, she concluded.