On October 2, the U.S. Food and Drug Administration (FDA) approved pirtobrutinib (Jaypirca) for adult patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with no known 17p deletion.
Efficacy and Safety
Efficacy was evaluated in the randomized, open-label, active-controlled BRUIN CLL-313 trial (ClinicalTrials.gov identifier NCT05023980) in 282 patients with previously untreated CLL/SLL without deletion of chromosome 17p. In the study, patients were randomly assigned 1:1 to receive pirtobrutinib (n = 141) until disease progression or bendamustine plus a rituximab product (n = 141) for six cycles.
The main efficacy outcome measure was progression-free survival as assessed by an independent review committee. With an estimated median follow-up of 28 months, the median progression-free survival was not estimable in the pirtobrutinib arm and 33.5 months (95% confidence interval [CI] = 32.7 to not estimable) in the bendamustine and rituximab arm (hazard ratio [HR] = 0.20; 95% CI = 0.11–0.37; P < .0001). At the time of the primary analysis of progression-free survival, overall survival data were still immature. The median overall surival was not reached in either arm with a total of 13 deaths: 3 deaths (2.1%) in the pirtobrutinib arm and 10 deaths (7.1%) in the control arm.
The most common (≥ 20%) adverse reactions occurring in patients receiving pirtobrutinib were upper respiratory tract infections (27%), rash (22%), and COVID-19 (21%). The most common (> 10%) grade 3 or 4 laboratory abnormality was neutrophil count decrease. Serious adverse reactions occurred in 28% of patients taking pirtobrutinib.
The prescribing information includes warnings and precautions for infections, hemorrhage, cytopenias, cardiac arrythmias, secondary primary malignancies, hepatotoxicity, and embryo-fetal toxicity.
Recommended Dosage
The recommended pirtobrutinib dose is 200 mg orally once-daily until disease progression or unacceptable toxicity.
Pirtobrutinib previously received an Orphan Drug designation. The review was completed using the FDA’s Assessment Aid.
