FDA grants accelerated approval to pirtobrutinib for relapsed or refractory mantle cell lymphoma
Regulatory approval: On Jan 27, 2023, the FDA granted accelerated approval to pirtobrutinib (Jaypirca; Eli Lilly) for adults with relapsed or refractory mantle cell lymphoma after at least two prior lines of systemic therapy, including a BTK inhibitor. Approval was based on the single-arm BRUIN trial in BTK inhibitor–pretreated MCL (n=120), showing an overall response rate of 50% (13% complete responses) and an estimated median duration of response of 8.3 months.
FDA accelerated approval (regulatory news)
On Jan 27, 2023, the FDA granted accelerated approval to pirtobrutinib (Jaypirca; Eli Lilly and Company) for relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.
Supporting evidence
Efficacy was evaluated in BRUIN (NCT03740529), an open-label, multicenter, single-arm trial of pirtobrutinib monotherapy that enrolled 120 patients with MCL previously treated with a BTK inhibitor. Patients had a median of 3 prior lines of therapy; 93% had ≥2 prior lines. Prior BTK inhibitors included ibrutinib (67%), acalabrutinib (30%), and zanubrutinib (8%); 83% discontinued their last BTK inhibitor due to refractory/progressive disease. Pirtobrutinib was given 200 mg orally once daily until progression or unacceptable toxicity.
Primary endpoints were overall response rate (ORR) and duration of response (DOR) per independent review using Lugano criteria. ORR was 50% (95% CI, 41–59) with 13% complete responses. Estimated median DOR was 8.3 months (95% CI, 5.7–NE); estimated 6-month DOR rate was 65.3% (95% CI, 49.8–77.1).
Safety and dosing highlights
Common adverse reactions (≥15%) included fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Grade 3–4 lab abnormalities (≥10%) included decreased neutrophils, lymphocytes, and platelets. Label warnings include infections, hemorrhage, cytopenias, atrial fibrillation/flutter, and second primary malignancies. Recommended dose: 200 mg once daily.