FDA grants accelerated approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic lymphoma
Regulatory approval: On Dec 1, 2023, the FDA granted accelerated approval to pirtobrutinib (Jaypirca) for adults with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. Approval was supported by the single-arm BRUIN trial (n=108), with an independent review committee–assessed ORR of 72% and median duration of response of 12.2 months; all responses were partial.
FDA accelerated approval (Dec 1, 2023)
The US FDA granted accelerated approval to pirtobrutinib (Jaypirca; Eli Lilly and Company) for adults with CLL/SLL who have received ≥2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
Evidence supporting approval
Efficacy was evaluated in BRUIN (NCT03740529), an open-label, international, single-arm, multicohort trial including 108 patients with CLL/SLL meeting the above prior-therapy criteria. Patients had a median of 5 prior lines (range 2–11); 77% discontinued their last BTK inhibitor due to refractory or progressive disease. Pirtobrutinib was given 200 mg orally once daily until progression or unacceptable toxicity.
Primary efficacy outcomes were overall response rate (ORR) and duration of response (DOR) assessed by an independent review committee per 2018 iwCLL criteria. Reported ORR was 72% (95% CI, 63–80) and median DOR was 12.2 months (95% CI, 9.3–14.7). All responses were partial responses.
Safety highlights from labeling
Common adverse reactions (≥20%) included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3/4 lab abnormalities (>10%) included decreased neutrophils, anemia, and decreased platelets. Serious infections occurred in 32%, including fatal infections in 10%. Label warnings/precautions include infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.