Pirtobrutinib Demonstrates Durable Efficacy and Safety Among Patients With Covalent BTK Inhibitor Pretreated R/R MCL

Kami J. Maddocks, MD, James Cancer Hospital, Ohio State University, Columbus, Ohio, analyzes the updated greater than 3 year follow-up results of the phase 1/2 BRUIN trial on the efficacy and safety of pirtobrutinib among patients with high-risk heavily pre-treated relapsed/refractory (R/R) mantle cell lymphoma (MCL) with prior covalent Bruton's tyrosine kinase inhibitor (cBTKi) therapy.

Transcript: 

Hi, I'm Kami Maddocks from the James Cancer Hospital at Ohio State University, where I treat lymphoma. I'm here today to discuss a little bit about relapsed/refractory mantle cell lymphoma, including the presentation around pirtobrutinib in covalent BTK inhibitor pretreated mantle cell lymphoma with updated results of the subgroup analysis from the BRUIN study, with greater than 3 years of follow-up from the start of enrollment.

As a little bit of background, the BRUIN study was a phase 1/2 trial that enrolled patients with relapsed/refractory B-cell malignancies and treated them with the noncovalent, or reversible, BTK inhibitor, pirtobrutinib. Pirtobrutinib is a first-in-class noncovalent BTK inhibitor. This trial enrolled patients with relapsed/refractory B-cell malignancies, including those [who] had been exposed to prior covalent BTK.

As we reported in the Journal of Clinical Oncology earlier this year, patients with relapsed/refractory mantle cell lymphoma, who had received prior treatment with covalent BTK inhibitors, were treated with this pirtobrutinib in the phase 1/2 BRUIN trial. This included 90 patients previously treated with covalent BTK inhibitor, including a little over 80% of those who had gone off covalent BTK because of disease progression, the rest going off because of toxicity.

This reported [a] high overall response rate of close to 58%, and a median duration of response of 21.6 months. Updated at the summer meetings [were] the outcomes in these 90 patients with mantle cell lymphoma, including looking at outcomes by pre-specified subgroups. In these 90 patients, the median prior lines of therapy [were] 3, with a range of 1 to 8. This included patients with TP53 mutations, high Ki67, and blastoid or pleomorphic morphology.

Overall response was 57%, with a complete response rate of 19% at longer follow-up. Median duration of response [was] 17.6 months, PFS [was] 7.4 months, and overall survival [was] near 2 years. [The] most common toxicities were fatigue, diarrhea, and anemia.

Looking at responses by pre-specified subgroups, pirtobrutinib appeared to be efficacious in high-risk subgroups. So, patients with blastoid or pleomorphic disease had similar overall response rates, and duration of response as to those with classical histology. 

Patients with TP53 mutation had [a] similar overall response and median duration of response to those with non-TP53 mutated disease, and patients with a high Ki67, as defined as a Ki67 to 30% or higher, had similar overall responses and median duration of response to those patients who had lower Ki67, suggesting that this agent does have activity across high-risk subtypes of mantle cell lymphoma.

Source:

Shah NN, Jurczak W, Maddocks KJ, et al. Pirtobrutinib in covalent BTK-inhibitor (cBTKi) pre-treated mantle cell lymphoma (MCL): Updated results and subgroup analysis from the phase 1/2 BRUIN study with >3 years follow-up from start of enrollment. J Clin Oncol. 2023;41(16_suppl):7514-7514. doi:10.1200/jco.2023.41.16