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 3 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 at ClinicalTrials.gov as #NCT03336333.

1st Department of Medicine 1st Faculty of Medicine Charles University General Hospital Prague Czech Republic

4th Department of Internal Medicine Hematology University Hospital Hradec Kralove Czech Republic; Faculty of Medicine Charles University Prague Czech Republic

ASST Grande Ospedale Metropolitano Niguarda Milan

BeiGene USA Inc San Mateo CA

Calvary Mater Newcastle Waratah NSW

Concord Repatriation General Hospital Concord NSW Australia; University of Sydney Concord NSW

Copernicus Wojewódzkie Centrum Onkologii Gdánsk

Dana Farber Cancer Institute Boston MA

Department of Haematology Christchurch Hospital Christchurch

Department of Oncology Pathology Karolinska Institutet Stockholm Sweden; Department of Hematology Karolinska University Hospital Stockholm

Fondazione Policlinico Universitario A Gemelli IRCCS Rome

Fred Hutchinson Cancer Research Center Seattle WA USA; Department of Medicine University of Washington Seattle WA

Hematology Unit Santa Maria delle Croci Hospital Ravenna

Medical University of Lodz Lodz

Monash Health Clayton Victoria Australia; Monash University Clayton Victoria

North Shore Hospital Auckland

Peninsula Private Hospital Frankston Victoria

Peter MacCallum Cancer Centre Melbourne Victoria Australia; University of Melbourne Parkville Victoria Australia; Royal Melbourne Hospital Parkville Victoria Australia; St Vincent's Hospital Melbourne Fitzroy Victoria

St James's University Hospital Leeds

Università Vita Salute San Raffaele and IRCCS Ospedale San Raffaele Milano

Washington University School of Medicine St Louis MO

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Opinion: What defines high-risk CLL in the post-chemoimmunotherapy era?

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ClinicalTrials.gov
NCT03336333