On January 27, 2023, the FDA accelerated the approval of pirtobrutinib (Jaypirca; Eli Lilly) for the treatment of patients with relapsed or refractory mantle-cell lymphoma (MCL) after at least 2 lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. The FDA granted this indication an orphan drug designation.
This approval was based on results of the BRUIN study, an open-label, multicenter, single-arm clinical trial with pirtobrutinib monotherapy. The study included 120 patients with MCL who had received a BTK inhibitor; 93% of them received ≥2 previous lines of BTK inhibition, including ibrutinib (Imbruvica; 67%), acalabrutinib (Calquence; 30%), or zanubrutinib (Brukinsa; 8%). In all, 83% of the patients had discontinued their last BTK inhibitor because of progressive or refractory disease. All patients received pirtobrutinib 200 mg orally once daily until disease progression or unacceptable adverse events.
The main efficacy measures were overall response rate (ORR) and duration of response (DOR). The ORR was 50% (95% confidence interval [CI], 41-59), with a 13% complete response rate. At 6 months, the estimated DOR rate was 65.3% (95% CI, 49.8-77.1), with an estimated median DOR of 8.3 months (95% CI, 5.7-not estimable).
The most common (≥15%) adverse reactions were fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. The most common (≥10%) grade 3 or 4 laboratory abnormalities were decreased neutrophil, lymphocyte, and platelet counts.
The prescribing information includes warnings about infections, hemorrhage, cytopenias, atrial fibrillation and flutter, and second primary malignancies.