In the BRUIN phase 1/2 study, patients were free to discontinue study treatment at any time. Patients were advised that they would be followed for survival after discontinuing treatment. Over the course of the BRUIN study, the investigator and/or the study sponsor were to remove a patient from treatment for any of the reasons listed below:

• progressive disease by disease-defined criteria. Patients with documented PD who tolerated study therapy and, in the opinion of the investigator, were deriving clinical benefit from continuing study treatment, were allowed to continue treatment with documented approval from the sponsor
• unacceptable toxicity
• intercurrent illness compromising ability to fulfill protocol requirements
• pregnancy
• requirement for alternative treatment in the opinion of the investigator, unless such treatment was temporary (eg, local radiation or surgery for disease that did not meet the definition of progressive disease)
• dose delay >28 days, unless a clinical need for prolonged delay had been determined by the investigator with documented approval from the sponsor
• significant noncompliance with the study protocol
• withdrawal of consent by the patient
• loss to follow-up
• death, or
• study termination by the sponsor.3 

As of the data cutoff date of January 31, 2022, the BRUIN trial enrolled 725 patients for treatment with pirtobrutinib monotherapy. Of 725 patients, 164 were patients with mantle cell lymphoma (MCL).4 The study assessed safety in 128 patients with MCL who had received pirtobrutinib 200 mg monotherapy and a prior Bruton's tyrosine kinase (BTK) inhibitor.1

Of the 128 patients with MCL included in the safety population, 12 patients (9.4%) discontinued study treatment due to an adverse event (AE) (Adverse Events Leading to Treatment Discontinuation in >1% Patients With MCL in the BRUIN Phase 1/2 Study).1,5

As of the data cut-off date on February 8, 2023, 778 patients had been enrolled in the BRUIN trial for treatment with pirtobrutinib monotherapy, of which 317 were patients CLL or SLL.5 Among these patients with CLL/SLL, an analysis was conducted in the subset of patients who received a starting dose of pirtobrutinib 200 mg monotherapy once daily and treatment with ≥2 prior lines of therapy, including a BTK inhibitor and B-cell lymphoma-2 (BCL-2) inhibitor.1,5

Of the 110 patients with CLL/SLL included in the safety population, 10 patients (9.1%) discontinued study treatment due to an AE (Adverse Events Leading to Treatment Discontinuation in >1% Patients With CLL/SLL in the BRUIN Phase 1/2 Study).1,5

As of the data cutoff date of July 29, 2022, the BRUIN trial enrolled 773 patients for treatment with pirtobrutinib monotherapy. A safety analysis was conducted for the overall pirtobrutinib monotherapy dataset which was defined as all enrolled MCL, CLL/SLL, and NHL patients from phase 1 and phase 2 of the BRUIN study who received ≥1 dose of pirtobrutinib.5,6

Of the 773 patients included in the overall safety population, 20 patients (2.6%) discontinued study treatment due to a treatment-related AE.7

Discontinuation of study treatment due to treatment-emergent AEs in all patients in the BRUIN trial is summarized in Treatment-Emergent Adverse Events Leading to Treatment Discontinuation in All Patients in the BRUIN Phase 1/2 Study. Adverse Events of Special Interest Leading to Treatment Discontinuation in All Patients in the BRUIN Phase 1/2 Study summarizes the rates of discontinuation in patients who reported AEs of special interest which were defined as AEs previously associated with covalent BTK inhibitors.