Dr Woyach on Responses to Pirtobrutinib in CLL/SLL With/Without Prior BCL2 Inhibitor Exposure

Jennifer A Woyach, MD, hematologist-oncologist, professor, Division of Hematology, the Ohio State University Comprehensive Cancer Center– James, discusses the efficacy of pirtobrutinib (Jaypirca) in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who progressed on treatment with a covalent BTK inhibitor, including subgroups with or without previous exposure to a BCL2 inhibitor, from the phase 1/2 BRUIN study (NCT03740529).

The BRUIN trial was a dose-escalation and -expansion study of pirtobrutinib monotherapy in adult patients with MCL (n = 166), CLL/SLL (n = 317), and other histologic subtypes (n = 295), Woyach begins. A total of 282 patients with CLL/SLL who previously been treated with a covalent BTK inhibitor were included in this analysis, including 128 who had previously received BCL2 inhibitors, Woyach details.

Updated findings presented at the 2023 ASH Annual Meeting showed that treatment with pirtobrutinib produced an objective response rate (ORR) of 81.6% (95% CI, 76.5%-85.9%) at a median follow-up of 30 months, Woyach reports. This included a complete response rate of 1.8%, a nodular partial response (nPR) of 0.7%, a partial response (PR) of 69.5%, and a PR with lymphocytosis of 9.6%.

ORRs achieved with the agent were comparable in patients with and without prior exposure to BCL-2 inhibitors, Woyach notes. In BCL-2 inhibitor–naive patients, the ORR was 83.1% (95% CI, 76.2%-88.7%) vs 79.7% (95% CI, 71.7%-86.3%) in those with prior exposure.

Additionally, the median progression-free survival (PFS) with pirtobrutinib in patients who previously received covalent BTK inhibitors was 19.4 months (95% CI, 16.6-22.1), Woyach states. Median PFS in the BCL-2 inhibitor–naive group was 23.0 months (95% CI, 19.6-28.4) compared with 15.9 months (95% CI, 13.6-17.5) in the BCL-2 inhibitor–exposed group.

Responses to pirtobrutinib were not significantly influenced by age, performance status, prior therapies, or reasons for prior BTK inhibitor discontinuation. High-risk genomic factors, including resistance mutations to BTK, were not found to predict responses with pirtobrutinib, Woyachadds.

There were no new safety signals observed with pirtobrutinib, Woyach notes. The agent produced a low rate of treatment-emergent adverse effects, Woyach says, adding that its toxicity profile was comparable with that of other BTK inhibitors. These results demonstrate the promising and durable responses achieved with pirtobrutinib in this subgroup, she concludes.