Please use this identifier to cite or link to this item: https://repository.monashhealth.org/monashhealthjspui/handle/1/37792
Conference/Presentation Title: Pooled analysis of safety data from zanubrutinib (BGB-3111) monotherapy studies in hematologic malignancies.
Authors: Opat S. ;Roberts A.W.;Cull G.;Tam C.S.;Trotman J.;Simpson D.;Ritchie D.;Verner E.;Ratnasingam S.;Anderson M.A.;Wood P. ;Seymour J.F.;Zhu J.;Li J.;Marlton P.;Gottlieb D.;Lin L.;Ro S.;Hilger J.;Wang A.;Xu X.;Ji M.
Institution: (Tam, Ritchie, Seymour) Peter MacCallum Cancer Center, East Melbourne, VIC, Australia (Tam, Ritchie, Anderson, Seymour, Roberts) University of Melbourne, Parkville, VIC, Australia (Tam) St Vincent's Hospital, Fitzroy, VIC, Australia (Trotman, Verner) Concord Repatriation General Hospital, Concord, Australia (Trotman, Anderson) University of Sydney, Concord, Australia (Simpson) North Shore Hospital, Auckland, New Zealand (Ratnasingam, Opat) Monash Health, Clayton, VIC, Australia (Wood, Marlton) Princess Alexandra Hospital, Brisbane, Australia (Wood, Marlton) University of Queensland, School of Medicine, Brisbane, Australia (Zhu) Beijing Cancer Hospital, Beijing, China (Li) Jiangsu Province Hospital, Nanjing, China (Gottlieb) University of Sydney, Westmead Hospital, Westmead, Australia (Lin, Ro, Hilger, Wang, Xu, Ji) Beigene (Beijing) Co. Ltd., Beijing, China (Lin, Ro, Hilger, Wang, Xu, Ji) Beigene (Beijing) Co. Ltd., Emeryville, CA, United States (Roberts) Royal Melbourne Hospital, Parkville, VIC, Australia (Opat) Monash University, Clayton, VIC, Australia (Cull) Sir Charles Gairdner Hospital, Perth, Western Australia, Australia (Cull) University of Western Australia, Perth, Australia
Presentation/Conference Date: 17-Jan-2019
Copyright year: 2018
Publisher: Wolters Kluwer Health
Publication information: HemaSphere. Conference: 23rd Congress of the European Hematology Association, EHA 2018. Stockholm Sweden. 2 (Supplement 2) (pp 176-177), 2018. Date of Publication: June 2018.
Abstract: Background: Bruton's tyrosine kinase (BTK) plays a critical role in B-cell receptor signaling, which mediates B-cell proliferation, migration and adhesion. Zanubrutinib is a potent, selective and irreversible BTK inhibitor. It has demonstrated profound BTK inhibition with minimal inhibition of offtarget kinases such as EGFR, ITK, JAK3, HER2, and TEC, providing a good scientific rationale for a reduced toxicity profile. Aim(s): To demonstrate the safety profile of zanubrutinib. Method(s): Safety data from patients (pts) in 6 ongoing zanubrutinib monotherapy studies were analyzed. All pts have been treated with >=1 dose of oral (po) zanubrutinib at 40 mg once-daily to 160 mg twice-daily (bid). The analysis included frequency and severity of adverse events (AEs), AEs of special interest, and AEs leading to treatment discontinuation. Result(s): A total of 424 pts were included in the pooled analysis, with a data cutoff date of September 15, 2017. The median age was 64 years (range 20- 87) and 71.9% were males. The median follow-up duration was 4.8 months (range 0.03-36.0). The most common (occurring in >=10% of pts) AEs were upper respiratory tract infection (23.8%), contusion (17.5%), diarrhea (14.2%), cough (13.0%), rash (12.7%), anemia (11.8%), and neutrophil count decreased (11.6%). Serious AEs (SAEs) were reported in 24.3%, including 7.5% that were assessed as related to zanubrutinib. The most common SAEs included pneumonia (3.5%), lung infection (1.7%) and febrile neutropenia (1.2%). AEs of special interest are shown in the Table 1. The most common bleeding events included contusion (17.5%) and hematuria (8.3%). Major hemorrhage, defined as serious or Grade >=3 bleeding of any site, or central nervous system bleeding of any grade included gastrointestinal hemorrhage, purpura (0.5% each), melena, hemorrhagic cystitis, hematuria, renal hematoma, cerebral hemorrhage and hemothorax (0.2% each). The median time to first major hemorrhage was 23 days (range 3-262). The fatal event of cerebral hemorrhage was reported in a 70 year old male pt with mantle cell lymphoma who developed left occipital lobe hemorrhage after treatment with zanubrutinib 160 mg bid for 6 days. Amongst pts with atrial fibrillation/flutter (8 pts) a majority had known risk factors including hypertension (2 pts), pre-existing cardiovascular disease (2 pts) and concurrent infection (1 pt). The rates of Grade >=3 infections were 10.1 events/100 pts in the first 3 months, 3.1 in months 3 to 6, and 5.5 after 6 months. The most common second primary malignancies included basal cell carcinoma (3.5%) and squamous cell carcinoma of skin (2.8%) with 2.1% of pts having a prior history of skin cancer. AEs led to treatment discontinuation in 5.9% of pts with 2.4% related to zanubrutinib. Summary and Conclusion(s): Zanubrutinib has shown a favorable safety and tolerability profile in pts with various B-cell malignancies. In zanubrutinib's cumulative safety experience, events of interest with BTK inhibitors, such as atrial fibrillation (1.9%), major hemorrhage (2.1%), and severe diarrhea (0.7%) have been infrequent. Additionally, treatment discontinuation due to zanubrutinib-related adverse events was uncommon (2.4% of pts). These data suggest that exposure levels of zanubrutinib resulting in complete and sustained BTK inhibition can be safely achieved, resulting in low tolerability- related treatment failure rates. (Table Presented).
Conference Start Date: 2018-06-14
Conference End Date: 2018-06-17
DOI: http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1097/HS9.0000000000000060
ISSN: 2572-9241
URI: https://repository.monashhealth.org/monashhealthjspui/handle/1/37792
Type: Conference Abstract
Type of Clinical Study or Trial: Systematic review and/or meta-analysis
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