Dr Bhat on Choosing Between Pirtobrutinib and Liso-Cel for R/R CLL Management

“How do we choose pirtobrutinib vs CAR T-cell therapy? We look at certain [factors like] the logistics, patient characteristics, [and] comorbidities.”

Seema A. Bhat, MD, a hematologist at The Ohio State University Comprehensive Cancer Center—James; as well as an assistant professor in the Department of Internal Medicine in the Division of Hematology at The Ohio State University, discussed factors that she considers when choosing between pirtobrutinib (Jaypirca) and CAR T-cell therapy for the treatment of patients with double-refractory chronic lymphocytic leukemia (CLL).

The CAR T-cell therapy lisocabtagene maraleucel (liso-cel; Breyanzi) is now an FDA-approved treatment modality for patients with CLL and represents the only agent in this class approved for this indication, Bhat began. The FDA granted approval for liso-cel in patients with CLL who are considered “dual-refractory,” meaning they have previously been treated with at least 2 prior lines of therapy, including both a covalent BTK inhibitor and a BCL-2 inhibitor. This indication is similar to that for pirtobrutinib, which is also FDA approved for patients with CLL in the third-line setting following treatment with a BTK inhibitor and a BCL-2 inhibitor, Bhat explained.

Ongoing investigations continue to explore ways to optimize outcomes with CAR T-cell therapy in patients with CLL, Bhat said. Notably, an update from the phase 1/2 TRANSCEND CLL 004 study (NCT03331198)—the trial that led to liso-cel’s FDA approval in CLL—was presented at the 2024 ASH Annual Meeting, she highlighted. In the update, liso-cel had enhanced efficacy when administered concurrently with the BTK inhibitor ibrutinib (Imbruvica). Treatment with the combination resulted in a doubling of complete response (CR) rates, a particularly promising finding that highlights the potential of this synergistic strategy, according to Bhat.

When selecting between pirtobrutinib and CAR T-cell therapy for patients with CLL who have progressed following covalent BTK inhibition and venetoclax (Venclexta), several clinical factors should be considered, Bhat emphasized. These include treatment logistics, the patient’s overall fitness, and the presence or absence of comorbidities, she noted. For instance, in a younger, fit patient with no significant comorbid conditions and access to a specialized treatment center offering CAR T-cell therapy, liso-cel may be preferred due to the potential for durable remissions, she stated. The TRANSCEND-CLL-004 trial has shown that patients achieving CRs with liso-cel often experience sustained disease control, she added.

Conversely, for patients who are medically frail, have multiple comorbidities, or are unable or unwilling to travel to a center that offers this modality, pirtobrutinib may be a more feasible treatment option, Bhat reported. Additionally, in scenarios involving rapidly progressing disease, initiating CAR T-cell therapy may not be practical due to the manufacturing timeline of this therapy, which can take approximately 3 to 4 weeks, she continued. In such urgent clinical contexts, immediate initiation of pirtobrutinib may be warranted to control disease progression and bridge to other potential therapies, Bhat concluded.