Dr Rhodes on the Efficacy of Pirtobrutinib in Pretreated CLL/SLL

Joanna M. Rhodes, MD, MSCE, director, Lymphoma Program, system head, Lymphoma, assistant professor, medicine, Rutgers Robert Wood Johnson Medical School, RWJBarnabas Health, discusses the safety and efficacy of treatment with pirtobrutinib (Jaypirca) following exposure to a covalent BTK inhibitor in heavily pretreated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Investigators evaluated the efficacy and safety of the study drug in this patient population in the phase 1/2 BRUIN study (NCT03740529), findings from which were presented at the 2023 ASH Annual Meeting and supported the December 2023 FDA approval of pirtobrutinib for patients with CLL/SLL who have received at least 2 prior lines of therapy, including a BTK inhibitor and a BCL2 inhibitor. A long-term follow-up analysis of this trial stratified patients based on whether they were BCL2 inhibitor–naive or had undergone prior BCL2 inhibitor therapy, Rhodes begins. When examining these 2 cohorts, a notable difference emerged: patients without prior BCL2 inhibitor exposure had received fewer median prior lines of therapy compared with those who had received a prior BCL2 inhibitor, who had received a median of 5 prior lines of therapy, she states. In this analysis, investigators evaluated overall response rates, durability of responses, and median progression-free survival (PFS), Rhodes notes.

Notably, patients without prior BCL2 inhibitor exposure who received pirtobrutinib experienced a longer median PFS vs those with a history of BCL2 inhibitor therapy, she continues. This finding aligns with expectations about the sequencing of therapies, where later lines of therapy in CLL and other indolent non-Hodgkin lymphomas often have shorter durations, she elucidates.

Furthermore, the safety profile of pirtobrutinib was characterized by a lack of significant adverse effects (AEs), Rhodes continues. Few grade 3 or higher AEs were reported, with no grade 5 AEs and few grade 4 AEs, she emphasizes. The most common AEs included fatigue, diarrhea, and manageable grade 3 neutropenia, typically addressed with growth factors in clinical practice, Rhodes states. Patients on this study often reported minimal awareness of taking the drug, with one patient expressing a strong preference for pirtobrutinib over other agents, she emphasized. The manageable safety profile of pirtobrutinib underscores the efficacy of this drug’s on-target BTK inhibition, which results in few off-target effects and contributes to the drug's favorable tolerability, Rhodes concludes.