Dr Bhat on Selecting Between Liso-Cel and Pirtobrutinib in Relapsed/Refractory CLL

“Pirtobrutinib may be a better option [compared with liso-cel] for patients who have rapid [disease] progression where there is limited time to manufacture the CAR T-cell therapy.”

Seema A. Bhat, MD, associate professor, Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center—James, discussed considerations for selecting between lisocabtagene maraleucel (liso-cel; Breyanzi) and pirtobrutinib (Jaypirca) for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL).

In March 2024, the FDA approved liso-cel for the treatment of adult patients with CLL or small lymphocytic lymphoma (SLL) who received at least 2 previous lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. Data from the phase 1/2 TRANSCEND CLL 004 study (NCT03331198), which supported the approval, demonstrated that patients who were treated with liso-cel (n = 65) experienced a complete response (CR) rate of 20% (95% CI, 11.1%-31.8%). Patients with a CR had a median duration of response (DOR) that was not reached (NR; 95% CI, 15 months-NR).

In December 2023, the FDA also approved pirtobrutinib for the treatment of adult patients with CLL or SLL who received at least 2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. The regulatory decision was supported by data from the phase 1/2 BRUIN trial (NCT03740529). Patients treated with pirtobrutinib in BRUIN (n = 108) achieved an overall response rate of 72% (95% CI, 63%-80%), with a median DOR of 12.2 months (95% CI, 9.3-14.7) and a median time to response of 3.7 months (range, 1.7-27.9).

The FDA approvals of liso-cel and pirtobrutinib were important for patients with dual-refractory disease, as these patients do not have many effective treatment options, Bhat said. Safety is one of the most important considerations when selecting between the 2 agents, she continued. Pirtobrutinib is a well-tolerated, orally administered agent, although it must be administered on a continuous basis, she continued.

CAR T-cell therapies such as liso-cel are associated with significant adverse effects, such as cytokine release syndrome and neurotoxicity, and must be administered at specialized centers, Bhat noted. Patients must also be fit enough to receive lymphodepleting therapy, she added.

Other considerations when choosing between the 2 agents include disease bulk and the amount of time it takes to manufacture the CAR T cells, Bhat explained. Pirtobrutinib could be a better option for patients with rapid disease progression who cannot wait for liso-cel to be manufactured, she concluded.