Page 268 - Haematologica Vol. 109 - July 2024

LETTER TO THE EDITOR
afib/flutter with zanubrutinib, despite extended exposure, is important for long-term treatment. Additionally, a lower incidence of afib may minimize the need for supportive care (e.g., anticoagulants, antiplatelet agents) that can further increase the bleeding risk associated with BTKi. Finally, although hypertension in patients receiving ibrutinib has been associated with increased incidence of major cardio- vascular AE,7 the incidence of cardiac disorder TEAE was comparable for zanubrutinib across ALPINE, ASPEN, and SEQUOIA despite the higher hypertension EAIR observed in ALPINE.
Due to the continuous dosing of BTKi in most B-cell malig- nancies, low treatment discontinuation rates and long-term tolerability are key considerations, particularly in patients with B-cell malignancies such as chronic lymphocytic leuke- mia/small lymphocytic lymphoma who tend to be aged >65 years and have other (e.g., cardiovascular) comorbidities.8,9 The first-in-class BTKi ibrutinib has drastically improved treatment of numerous B-cell malignancies, but cardiac arrhythmias and their associated outcomes are a frequently cited concern10-12 and are possibly due to off-target inhibi- tion of kinases such as TEC and CSK.13,14 Such toxicities can limit the duration and, consequently, the benefit15 of treat- ment. Zanubrutinib was designed with greater selectivity to minimize off-target effects. In this analysis, zanubruti- nib remained well tolerated, consistent with the previous analysis,1 with no emergence of new safety signals, even at a median treatment duration of approximately 3 years. In the comparative analysis, zanubrutinib exhibited a more favorable safety profile than ibrutinib, as demonstrated by the longer median treatment duration and lower frequency of TEAE, including cardiac disorders, that led to treatment discontinuation or death. These analyses support zanu- brutinib as an appropriate long-term treatment option for patients with B-cell malignancies.
Authors
Jennifer R. Brown,1 Paolo Ghia,2 Wojciech Jurczak,3 Brad S. Kahl,4 Nicole Lamanna,5 Tadeusz Robak,6 Mazyar Shadman,7 Constantine S. Tam,8 Lugui Qiu,9 Jason Paik,10 Tommi Salmi,11 Liping Wang,12 Jun Zhang,10 Meng Zhang,10° Aileen Cohen,10 Han Ma10 and Alessandra Tedeschi13
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; 2Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy; 3Maria Skłodowska-Curie National Research Institute of Oncology, Kraków, Poland; 4Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, USA; 5Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA; 6Medical University of Łódź, Łódź, Poland; 7Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 8Alfred Hospital and Monash University, Melbourne, Victoria, Australia; 9State Key Laboratory of Experimental Hematology,
National Clinical Medical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China; 10BeiGene USA, Inc, San Mateo, CA, USA; 11BeiGene International GmbH, Basel, Switzerland; 12BeiGene (Shanghai) Co, Ltd, Shanghai, China and 13ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
°Current address: ProKidney Corp., Winston-Salem, NC, USA.
Correspondence:
J.R. BROWN - Jennifer_Brown@dfci.harvard.edu
https://doi.org/10.3324/haematol.2023.283846
Received: September 5, 2023. Accepted: February 14, 2024. Early view: February 29, 2024.
©2024 Ferrata Storti Foundation Published under a CC BY-NC license
Disclosures
JRB discloses consultancy for AbbVie, Acerta/AstraZeneca, Alloplex Biotherapeutics, BeiGene, Galapagos NV, Genentech/Roche, Grifols Worldwide Operations, InnoCare Pharma Inc, iOnctura, Kite, Loxo/ Lilly, Merck, Numab Therapeutics, Pfizer and Pharmacyclics; research funding from BeiGene, Gilead, iOnctura, Loxo/Lilly, MEI Pharma and TG Therapeutics. PG discloses honoraria from AbbVie, ArQule/MSD, AstraZeneca, BeiGene, Celgene/Juno/Bristol Myers Squibb, Janssen, Lilly/Loxo, MEI Pharma, Roche and Sanofi; research funding from AbbVie, AstraZeneca, Janssen and Sunesis. WJ discloses consultancy for Janssen, AstraZeneca, MEI Pharma, Lilly, Takeda, Roche, AbbVie and BeiGene; research funding from AbbVie, Bayer, BeiGene, Celgene, Janssen, Roche, Takeda, TG Therapeutics, AstraZeneca, MEI Pharma and Lilly. BSK discloses research funding from BeiGene to Washington University School of Medicine (St Louis, MO, USA); consulting fees from AbbVie, AstraZeneca, BeiGene, Janssen and Pharmacyclics. NL discloses consultancy for AbbVie, AstraZeneca, BeiGene, Lilly/Loxo, Genentech, Janssen and Pharmacyclics; research funding from AbbVie, AstraZeneca, BeiGene, Lilly/Loxo, Genentech, Octapharma, Oncternal, MingSight and TG Therapeutics. TR discloses research funding from BeiGene, Octapharma, AstraZeneca, Janssen, Regeneron and GSK; honoraria from AstraZeneca, BeiGene, Janssen, AbbVie, Octapharma, Regeneron and GSK; travel, accommodations, expenses from AstraZeneca. MS discloses consultancy for AbbVie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, BeiGene, Bristol Myers Squibb, MorphoSys/Incyte, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Lilly, Adaptimmune, Mustang Bio, Regeneron, Merck, Fate Therapeutics, MEI Pharma and Atara Biotherapeutic; research funding from Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, AbbVie, TG Therapeutics, BeiGene, AstraZeneca, Sunesis, Atara
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