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Ferrata Storti Foundation
Haematologica 2021 Volume 106(9):2354-2363
Zanubrutinib monotherapy for patients with treatment-naïve chronic lymphocytic leukemia and 17p deletion
Constantine S. Tam,1,2,3,4 Tadeusz Robak,5 Paolo Ghia,6 Brad S. Kahl,7
Patricia Walker,8 Wojciech Janowski,9 David Simpson,10,11 Mazyar Shadman,12,13 Peter S. Ganly,14 Luca Laurenti,15 Stephen Opat,16,17
Monica Tani,18 Hanna Ciepluch,19 Emma Verner,20,21 Martin Šimkovič,22,23 Anders Österborg,24,25 Marek Trněný,26 Alessandra Tedeschi,27 Jason C. Paik,11 Sowmya B. Kuwahara,11 Shibao Feng,11 Vanitha Ramakrishnan,11 Aileen Cohen,11 Jane Huang,11 Peter Hillmen28 and Jennifer R. Brown29
1Peter MacCallum Cancer Center, Melbourne, Victoria, Australia; 2University of Melbourne, Parkville, Victoria, Australia; 3Royal Melbourne Hospital, Parkville, Victoria, Australia; 4St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia; 5Medical University of Lodz, Lodz, Poland; 6Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milano, Italy; 7Washington University School of Medicine, St Louis, MO, USA; 8Peninsula Private Hospital, Frankston, Victoria, Australia; 9Calvary Mater Newcastle, Waratah, New South Wales, Australia; 10North Shore Hospital, Auckland, New Zealand; 11BeiGene USA, Inc., San Mateo, CA, USA; 12Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 13Department of Medicine, University of Washington, Seattle, WA, USA; 14Department of Hematology, Christchurch Hospital, Christchurch, New Zealand; 15Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; 16Monash Health, Clayton, Victoria, Australia; 17Monash University, Clayton, Victoria, Australia; 18Hematology Unit, Santa Maria delle Croci Hospital, Ravenna, Italy; 19Copernicus Wojewódzkie Centrum Onkologii, Gdánsk, Poland; 20Concord Repatriation General Hospital, Concord, New South Wales, Australia; 21University of Sydney, Concord, New South Wales, Australia; 22Fourth Department of Internal Medicine - Hematology, University Hospital, Hradec Kralove, Czech Republic; 23Faculty of Medicine, Charles University, Prague, Czech Republic; 24Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; 25Department of Hematology, Karolinska University Hospital, Stockholm, Sweden; 26First Department of Medicine, First Faculty of Medicine, Charles University, General Hospital, Prague, Czech Republic; 27ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; 28St James’s University Hospital, Leeds, UK and 29Dana-Farber Cancer Institute, Boston, MA, USA
ABSTRACT
Patients with chronic lymphocytic leukemia or small lymphocytic lym- phoma 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 zanubruti- nib 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 treat- ment 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 hematolog- ic 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%), neu- tropenia/neutrophil count decreased (17.4%), and diarrhea (16.5%). Grade ≥ 3 adverse events were reported in 53 patients (48.6%), most commonly neu- tropenia (12.9%) and pneumonia (3.7%). An adverse event of atrial fibrillation was reported in three patients (2.8%). Zanubrutinib was active and well tol- erated in this large, prospectively enrolled treatment cohort of previously untreated patients with del(17p) chronic lymphocytic leukemia/small lym- phocytic lymphoma. This trial was registered as clinicaltrials.gov Identifier: NCT03336333.
Chronic Lymphocytic Leukemia
Correspondence:
CONSTANTINE S. TAM
constantine.tam@petermac.org
Received: May 29, 2020. Accepted: September 17, 2020. Pre-published: October 13, 2020.
https://doi.org/10.3324/haematol.2020.259432 ©2021 Ferrata Storti Foundation
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