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. Kuwahara,
Shibao Feng,
Vanitha Ramakrishnan,
Aileen Cohen,
Jane Huang,
Peter Hillmen,
Jennifer R. Brown
Affiliations
Constantine S. Tam
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
Tadeusz Robak
Medical University of Lodz, Lodz
Paolo Ghia
Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milano
Brad S. Kahl
Washington University School of Medicine, St Louis, MO
Patricia Walker
Peninsula Private Hospital, Frankston, Victoria
Wojciech Janowski
Calvary Mater Newcastle, Waratah, NSW
David Simpson
North Shore Hospital, Auckland
Mazyar Shadman
Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA
Peter S. Ganly
Department of Haematology, Christchurch Hospital, Christchurch
Luca Laurenti
Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome
Stephen Opat
Monash Health, Clayton, Victoria, Australia; Monash University, Clayton, Victoria
Monica Tani
Hematology Unit, Santa Maria delle Croci Hospital, Ravenna
Hanna Ciepluch
Copernicus Wojewódzkie Centrum Onkologii, Gdánsk
Emma Verner
Concord Repatriation General Hospital, Concord, NSW, Australia; University of Sydney, Concord, NSW
Martin Šimkovič
Fourth Department of Internal Medicine - Hematology, University Hospital, Hradec Kralove, Czech Republic; Faculty of Medicine, Charles University, Prague, Czech Republic
Anders Österborg
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Department of Hematology, Karolinska University Hospital, Stockholm
Marek Trněný
First Department of Medicine, First Faculty of Medicine, Charles University, General Hospital, Prague, Czech Republic
Alessandra Tedeschi
ASST Grande Ospedale Metropolitano Niguarda, Milan
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.