Zanubrutinib in relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study.
Yuqin SongKe-Shu ZhouDehui ZouJianfeng ZhouJianda HuHaiyan YangHuilai ZhangJie JiWei XuJie JinFangfang LvRu FengSujun GaoHaiyi GuoLei ZhouJane HuangWilliam NovotnyPil KimYiling YuBinghao WuJun ZhuPublished in: Blood (2022)
Bruton tyrosine kinase (BTK) inhibitor is an established treatment for relapsed/refractory (R/R) mantle cell lymphoma (MCL). Zanubrutinib, a highly selective BTK inhibitor, is approved for patients with MCL who have received ≥1 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 endpoint was the overall response rate (ORR), assessed per Lugano 2014. After a median follow-up of 35.3 months, the ORR was 83.7%, with 77.9% achieving complete response (CR); the 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 (OS) 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.
Keyphrases
- tyrosine kinase
- atrial fibrillation
- free survival
- open label
- epidermal growth factor receptor
- phase iii
- respiratory tract
- clinical trial
- phase ii
- acute lymphoblastic leukemia
- peripheral blood
- end stage renal disease
- study protocol
- acute myeloid leukemia
- diffuse large b cell lymphoma
- newly diagnosed
- multiple myeloma
- cell therapy
- heart failure
- catheter ablation
- chronic kidney disease
- hodgkin lymphoma
- physical activity
- single cell
- squamous cell carcinoma
- case report
- radiation therapy
- cross sectional
- double blind
- acute coronary syndrome
- stem cells
- mitral valve