Zanubrutinib in relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study

Yuqin Song, Keshu Zhou, Dehui Zou, Jianfeng Zhou, Jianda Hu, Haiyan Yang, Huilai Zhang, Jie Ji, Wei Xu, Jie Jin, Fangfang Lv, Ru Feng, Sujun Gao, Haiyi Guo, Lei Zhou, Jane Huang, William Novotny, Pil Kim, Yiling Yu, Binghao Wu, Jun Zhu, Yuqin Song, Keshu Zhou, Dehui Zou, Jianfeng Zhou, Jianda Hu, Haiyan Yang, Huilai Zhang, Jie Ji, Wei Xu, Jie Jin, Fangfang Lv, Ru Feng, Sujun Gao, Haiyi Guo, Lei Zhou, Jane Huang, William Novotny, Pil Kim, Yiling Yu, Binghao Wu, Jun Zhu

Abstract

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.

© 2022 by The American Society of Hematology.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Kaplan-Meier curves of survival and response analyses. (A) PFS as determined by investigator assessment. Shaded area indicates 95% CI. (B) OS. Shaded area indicates 95% CI. (C) PFS by best overall response. (D) OS by best overall response. SD, stable disease.
Figure 2.
Figure 2.
Most common treatment-emergent adverse events (≥10%) regardless of causality.
Figure 3.
Figure 3.
Mutation landscape in 54 Chinese patients with R/R MCL.

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