Zanubrutinib monotherapy for patients with treatment-naïve chronic lymphocytic leukemia and 17p deletion

Constantine S. Tam, Tadeusz Robak, Paolo Ghia, Brad S. Kahl, Patricia Walker, Wojciech Janowski, David Simpson, Mazyar Shadman, Peter S. Ganly, Luca Laurenti, Stephen Opat, Monica Tani, Hanna Ciepluch, Emma Verner, Martin Šimkovič, Anders Österborg, Marek Trněný, Alessandra Tedeschi, Jason C. Paik, Sowmya B. KuwaharaShibao Feng, Vanitha Ramakrishnan, Aileen Cohen, Jane Huang, Peter Hillmen, Jennifer R. Brown

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Patients with chronic lymphocytic leukemia or small lymphocytic lymphoma whose tumors carry deletion of chromosome 17p13.1 [del(17p)] have an unfavorable prognosis and respond poorly to standard chemoimmunotherapy. Zanubrutinib is a selective next-generation Bruton tyrosine kinase inhibitor. We evaluated the safety and efficacy of zanubrutinib 160 mg twice daily in treatment-naïve patients with del(17p) disease enrolled in a dedicated, nonrandomized cohort (Arm C) of the phase III SEQUOIA trial. A total of 109 patients (median age, 70 years; range, 42–86) with centrally confirmed del(17p) were enrolled and treated. After a median of 18.2 months (range, 5.0–26.3), seven patients had discontinued study treatment due to progressive disease, four due to an adverse event, and one due to withdrawal of consent. The overall response rate was 94.5% with 3.7% of patients achieving complete response with or without incomplete hematologic recovery. The estimated 18-month progression-free survival rate was 88.6% (95% CI: 79.0–94.0) and the estimated 18-month overall survival rate was 95.1% (95% CI: 88.4–98.0). Most common all-grade adverse events included contusion (20.2%), upper respiratory tract infection (19.3%), neutropenia/neutrophil count decreased (17.4%), and diarrhea (16.5%). Grade ≥ 3 adverse events were reported in 53 patients (48.6%), most commonly neutropenia (12.9%) and pneumonia (3.7%). An adverse event of atrial fibrillation was reported in three patients (2.8%). Zanubrutinib was active and well tolerated in this large, prospectively enrolled treatment cohort of previously untreated patients with del(17p) chronic lymphocytic leukemia/small lymphocytic lymphoma. This trial was registered as Identifier: NCT03336333.

Original languageEnglish
Pages (from-to)2354-2363
Number of pages10
Issue number9
StatePublished - Sep 2021


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