Updated results from the phase I/II BRUIN study showed that pirtobrutinib continues to be well tolerated and demonstrates promising and durable efficacy in heavily pretreated patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) who have been treated with a prior covalent Bruton’s tyrosine kinase (BTK) inhibitor.
The updated analysis with extended follow-up from the BRUIN trial was presented in a poster session at the 2022 American Society of Hematology Annual Meeting and Exposition by Michael L. Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues.
The study covered patients with previously treated B-cell malignancies, including MCL, who were eligible for treatment with pirtobrutinib monotherapy in either the dose-escalation or -expansion portion of the multicenter, phase I/II BRUIN study.
The response evaluable cohort consisted of the first 90 patients with MCL enrolled in either phase I or II who had measurable disease, had received a prior covalent BTK inhibitor-containing regimen, and had no known central nervous system involvement. The safety cohort consisted of all patients with B-cell malignancies who received at least one dose of pirtobrutinib monotherapy (n=725).
Among the 90 patients with MCL who had received a prior BTK inhibitor, the median age was 70 years (range, 46-87 years), and the median number of prior lines of therapy was three (range, 1-8 therapies). The majority of patients (82%; n=74) discontinued prior BTK inhibitor therapy due to disease progression.
Overall, 86% (n=77) received the recommended phase II dose of pirtobrutinib 200 mg once daily as the starting dose. In this group of heavily pretreated patients with R/R MCL, including all with prior BTK inhibitor use, the overall response rate (ORR) based on the Lugano 2014 criteria was 58% (95% CI, 47-68), including 18 complete responses (20%) and 34 partial responses (38%). Responses were observed in six of eight patients (75%) with blastoid MCL and in six of 12 patients (50%) with pleomorphic MCL.
At a median follow-up of 12 months, the median duration of response (DOR) among the 52 responding patients was 22 months (95% CI, 7.5-not estimable [NE]). The 12- and 18-month estimated DOR rates were 57% (95% CI, 39-72) and 52% (95% CI, 34-68), respectively.
Patients who discontinued their prior BTK inhibitor due to disease progression (n=74) had an ORR of 50% (95% CI, 38-62) and a median DOR of 14.8 months (95% CI, 5.6-NE).
“Pirtobrutinib continues to demonstrate promising and durable efficacy in heavily pre-treated R/R MCL patients who have been treated with a prior covalent BTK inhibitor,” the investigators concluded, adding that in terms of safety, “pirtobrutinib was well-tolerated with low-rates of discontinuation due to drug-related toxicity.”
Wang ML, Shih N, Jurczak W, et al. Efficacy of pirtobrutinib in covalent btk-inhibitor pre-treated relapsed/refractory mantle cell lymphoma: additional patients and extended follow-up from the phase 1/2 BRUIN study. Abstract #4218. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.