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BRUIN MCL-321 Focuses on Pirtobrutinib in BTK Inhibitor–Naive Mantle Cell Lymphoma

By: Julia Fiederlein
Posted: Friday, August 26, 2022

Researchers are currently recruiting patients for the global phase III BRUIN MCL-321 trial, which is comparing the noncovalent Bruton’s tyrosine kinase (BTK) inhibitor pirtobrutinib with the investigator’s choice of covalent BTK inhibitor therapy in patients with previously treated, BTK inhibitor–naive mantle cell lymphoma. Martin Dreyling, MD, PhD, of the LMU University Hospital, Munich, and colleagues shared the study design during the European Hematology Association (EHA) 2022 Congress (Abstract P1100).  

“Covalent BTK inhibitors…are not curative, and the majority of patients will require additional treatment,” the investigators remarked. “In the phase I/II BRUIN study, pirtobrutinib achieved pharmacokinetic exposures that exceeded its BTK IC96 at trough, was well tolerated, and demonstrated promising efficacy in heavily pretreated, poor-prognosis [patients with MCL], most of whom had prior treatment with a covalent BTK inhibitor.”

The investigators plan to enroll approximately 500 adults with confirmed, measurable mantle cell lymphoma who experienced disease progression or relapse following their last treatment. Those who have a history of current or prior central nervous system involvement, significant cardiovascular disease, stroke, or intracranial hemorrhage within 6 months of randomization, and allogeneic stem cell transplantation, autologous stem cell transplantation, or chimeric antigen receptor T-cell therapy within 60 days of randomization will be excluded.

Patients will be randomly assigned in a 1:1 ratio to receive pirtobrutinib or the investigator’s choice of ibrutinib, acalabrutinib, or zanubrutinib; they will be stratified by simplified Mantle Cell Lymphoma International Prognostic Index risk, the investigator’s choice of therapy, and the number of lines of prior treatment. The investigators identified independent review committee–assessed progression-free survival as the primary endpoint. Overall response, duration of response, investigator-assessed progression-free survival, overall survival, event-free survival, time to treatment failure, time to next treatment, progression-free survival 2, safety and tolerability, and patient-reported outcomes will be evaluated as secondary endpoints.

Disclosure: For full disclosures of the study authors, visit

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