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Clinical Trial
. 2022 May 26;139(21):3148-3158.
doi: 10.1182/blood.2021014162.

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

Yuqin Song  1 , Keshu Zhou  2 , Dehui Zou  3 , Jianfeng Zhou  4 , Jianda Hu  5 , Haiyan Yang  6 , Huilai Zhang  7 , Jie Ji  8 , Wei Xu  9 , Jie Jin  10 , Fangfang Lv  11 , Ru Feng  12 , Sujun Gao  13 , Haiyi Guo  14 , Lei Zhou  15 , Jane Huang  16 , William Novotny  16 , Pil Kim  16 , Yiling Yu  14 , Binghao Wu  14 , Jun Zhu  1
Affiliations
Clinical Trial

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

Yuqin Song et al. Blood. .

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.

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Figures

None
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.
See this image and copyright information in PMC

Comment in

  • A cauldron of choices.
    Kamdar M. Kamdar M. Blood. 2022 May 26;139(21):3103-3104. doi: 10.1182/blood.2022015995. Blood. 2022. PMID: 35616990 No abstract available.

References

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