Zanubrutinib in relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study
Mené sur 86 patients atteints d'un lymphome à cellules du manteau réfractaire ou récidivant (durée médiane de suivi : 35,3 mois), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité du zanubrutinib, un inhibiteur de tyrosine kinase de Bruton
Bruton tyrosine kinase (BTK) inhibitor is an established treatment for relapsed/refractory mantle cell lymphoma (R/R MCL). Zanubrutinib, a highly selective BTK inhibitor, is approved for patients with MCL who have received at least one prior therapy. We report the long-term safety and efficacy results from the multicenter, open-label, phase 2 registration trial of zanubrutinib. Patients (N = 86) received oral zanubrutinib 160 mg twice daily. The primary end point was overall response rate (ORR), assessed per Lugano 2014. After median follow-up of 35.3 months, the ORR was 83.7%, with 77.9% achieving complete response; median duration of response was not reached. Median progression-free survival (PFS) was 33.0 months (95% confidence interval [CI], 19.4-NE). The 36-month PFS and overall survival rates were 47.6% (95% CI, 36.2-58.1) and 74.8% (95% CI, 63.7-83.0), respectively. The safety profile was largely unchanged with extended follow-up. Most common (≥20%) all-grade adverse events (AEs) were neutrophil count decreased (46.5%), upper respiratory tract infection (38.4%), rash (36.0%), white blood cell count decreased (33.7%), and platelet count decreased (32.6%); most were grade 1/2 events. Most common (≥10%) grade ≥3 AEs were neutrophil count decreased (18.6%) and pneumonia (12.8%). Rates of infection, neutropenia, and bleeding were highest in the first 6 months of therapy and decreased thereafter. No cases of atrial fibrillation/flutter, grade ≥3 cardiac AEs, second primary malignancies, or tumor lysis syndrome were reported. After extended follow-up, zanubrutinib demonstrated durable responses and a favorable safety profile in R/R MCL. The trial is registered at ClinicalTrials.gov as NCT03206970.
Blood 2022