Dr Shah on Long-Term Survival Data For Pirtobrutinib in BTK Inhibitor–Pretreated R/R MCL

Nirav N. Shah, MD, associate professor, Medical College of Wisconsin, discusses the long-term efficacy of pirtobrutinib (Jaypirca) in patients with heavily pretreated, relapsed/refractory mantle cell lymphoma (MCL) with previous exposure to covalent BTK inhibitors, according to updated data from the phase 1/2 BRUIN (NCT03740529).

The BRUIN trial was a single-arm, open-label, multicenter trial evaluating the highly selective, non-covalent BTK inhibitor in patients with MCL, chronic lymphocytic leukemia, or other hematologic malignancies. Primary analysis of this trial was conducted in the first 90 enrolled patients with MCL who had measurable disease, had received a prior covalent BTK inhibitor, and had no known central nervous system involvement, Shah says. Previously reported findings showed that pirtobrutinib elicited clinically meaningful and durable response rates and had a favorable safety profile in this population.

These data supported the agent's accelerated approval for patients with relapsed/ refractory MCL following at least 2 lines of systemic therapy, including a BTK inhibitor, in January 2023.

Long-term survival data with the agent in this prespecified primary efficacy population were presented at the 2023 ASCO Annual Meeting alongside findings from an analysis of high-risk subgroups in this study, Shah states. At a median follow-up of approximately 2 years, patients who received pirtobrutinib had a median overall survival (OS) of 23.5 months, Shah reports. Overall response rate (ORR) was 56.7% and consisted of a complete response rate of 18.9% and a partial response rate of 37.8%. This ORR was comparable to previously reported response rates from BRUIN, Shah notes. The median duration of response (DOR) was 17.6 months. These data indicate that pirotbrutinib can not only improve OS but also maintain responses for long periods of time, Shah emphasizes.

Regarding safety, pirtobrutinib was well tolerated and was associated with a low rate of grade 3/4 adverse effects (AEs) and treatment-related discontinuations, Shah continues. Notably, there were also low rates of common BTK inhibitor–related AEs such as atrial fibrillation, cardiotoxicity, high blood pressure and bleeding, he adds. These data were in line with the regimen's toxicity profile in prior reports of the BRUIN study, Shah states.

Analysis of patients with blastoid/pleiomorphic variants, elevated Ki-67, and TP53 mutations, revealed that pirtobrutinib produced consistent ORRs regardless of the high-risk disease features expressed, Shah concludes.

Dr Shah reports serving as a consultant or in an advisory role for Incyte, Janssen Oncology, Juno/Bristol-Myers Sqibb, Kite, a Gilead company, Loxo/Lilly, Novartis, Seagen, TG Therapeutics; he received research funding from Adaptive Biotechnologies, Loxo/Lilly and Miltenyi Biotec; he has stock or other ownership interests with Tundra Targeted Therapeutics; his travel expenses were funded by Miltenyi Biotec