The non-covalent Bruton’s tyrosine kinase (BTK) inhibitor pirtobrutinib has promising efficacy and is tolerable in heavily pretreated patients with mantle cell lymphoma (MCL) and other non-Hodgkin lymphomas (NHLs), according to research presented at the 2021 British Society for Haematology annual meeting.

BTK inhibitors have marked efficacy in MCL and other NHLs, but many patients develop resistance or discontinue treatment for adverse events. Pirtobrutinib is a non-covalent BTK inhibitor that aims to overcome those limitations.

The BRUIN trial ( Identifier: NCT03740529) is a multicenter phase 1/2 trial to determine the safety and efficacy of pirtobrutinib. The trial enrolled patients with advanced B-cell malignancies who have had 2 or more previous therapies. This presentation focused on the results for patients with MCL, Waldenstrom macroglobulinemia (WM), and other NHLs.

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No dose limiting toxicities occurred in the trial. The most common adverse events were fatigue, diarrhea, and contusion. The phase 2 dose was set at 200 mg once daily.

A total of 56 patients with MCL were available for efficacy evaluation. The overall response rate (ORR) was 52%, with 14 complete responses, 15 partial responses, and 10 patients with stable disease after a median follow up of 6 months. The ORR was the same for patients previously treated with a BTK inhibitor.

A total of 55 patients with other NHLs include 25 patients with diffuse large B-cell lymphoma (DLBCL), 8 patients with follicular lymphoma (FL), 9 patients with marginal zone lymphoma (MZL), and 8 patients with Richter’s transformation (RT). Best ORRs seen with each disease type were as follows: DLBCL, 24%; FL, 50%; MZL, 22%; and RT, 75%. In 19 patients with WM, the best ORR was 68%. The ORR was similar for patients who were previously treated with a BTK inhibitor.

The authors concluded that pirtobrutinib has promising efficacy in patients with MCL who have received multiple prior treatments, including treatment with a covalent BTK inhibitor. It is also promising for patients with other NHLs, and is well-tolerated.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Eyre TA, Shah NN, Alencar AJ, et al. Pirtoburtinib (LOXO-305), a next generation highly selective non-covalent Bruton’s Tyrosine Kinase inhibitor in previously treated mantle cell lymphoma and other non-Hodgkin lymphomas: results from the phase 1/2 BRUIN study. Poster presented at: 2021 British Society for Haematology annual meeting; April 25-28, 2021; virtual.