TY - JOUR
T1 - Zanubrutinib in lymphoproliferative disorders
T2 - a comprehensive review
AU - Muñoz, Javier
AU - Wang, Yucai
AU - Jain, Preetesh
AU - Wang, Michael
N1 - Funding Information:
The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JM reports consultancy role with, research funding from, and speakers’ bureau for Pharmacyclics, Bayer, Gilead/Kite Pharma, Janssen, and Celgene; consultancy role with Pfizer, Alexion, Fosunkite, Innovent, Debiopharm, Epizyme, Karyopharm, and Genmab; consultancy role with Juno/Celgene; consultancy role with and speakers’ bureau for Bristol Myers Squibb, BeiGene; consultancy role with, honoraria from, and speakers’ bureau for Kyowa; consultancy role with, research funding from, honoraria from, and speakers’ bureau for Seattle Genetics; research funding from Merck, Portola, Incyte, and Millennium; research funding from and speakers’ bureau for Genentech; speakers’ bureau for Acrotech/Aurobindo, Verastem, AstraZeneca, Roche, and AbbVie. YW reports research funding from, and advisory role with Incyte and Loxo Oncology; research funding from InnoCare, Novartis, and Genentech; advisory role with Eli Lilly and TG therapeutics. PJ reports consultancy role with Eli Lilly, Incyte, Kite, research funding from AstraZeneca. MW reports research funding and honoraria from Acerta Pharma; consultancy role with, research funding, and honoraria from AstraZeneca, BeiGene, Janssen, and Kite Pharma; honoraria from Anticancer Association, CAHON, Chinese Medical Association, Clinical Care Options, Dava Oncology, Hebei Cancer Prevention Federation, Imbruvica, Imedex, Moffit Cancer Center, Mumbai Hematology Group, Newbridge Pharmaceuticals, OMI, Physicians Education Resources (PER), Scripps, and The First Affiliated Hospital of Zhejiang University; consultancy role with Bayer Healthcare, CSTone, DTRM Biopharma (Cayman) Limited, and Genentech; research funding from BioInvent, Celgene, and Molecular Templates; consultancy role with and honoraria from Epizyme and Miltenyi Biomedicine GmbH; consultancy role with and research funding from InnoCare, Juno, Loxo Oncology, Oncternal, Pharmacyclics, and VelosBio.
Funding Information:
This work, including medical writing and editorial assistance, was supported by BeiGene USA, Inc. Writing and editorial support were provided by Robert Rydzewski, MS, CMPP, and submission support was provided by Laura Leistikow, BFA, both of Bio Connections, LLC (Chicago, IL), supported by BeiGene USA, Inc. (San Mateo, CA).
Publisher Copyright:
© The Author(s), 2022.
PY - 2022
Y1 - 2022
N2 - The availability of Bruton tyrosine kinase (BTK) inhibitors has brought about a paradigm shift in the treatment of patients with B-cell lymphomas and chronic lymphocytic leukemia. BTK was clinically validated as a target by the efficacy of the first-in-class inhibitor ibrutinib. The extended survival conferred by BTK inhibitors has brought long-term tolerability to the foreground. To minimize toxicities thought to be attributable to off-target kinase inhibition, a next generation of BTK inhibitors with greater selectivity was developed. In the United States, zanubrutinib, a next-generation BTK inhibitor, has been approved for treating adults with mantle cell lymphoma who have received at least one prior therapy, for adults with Waldenström macroglobulinemia, and for adults with relapsed or refractory marginal zone lymphoma who have received at least one anti-CD20–based therapy. Because few head-to-head comparative trials of BTK inhibitors have so far been reported, no BTK ‘inhibitor of choice’ can be identified. Zanubrutinib has promising efficacy in its approved indications and appears to have reduced cardiac toxicities, particularly atrial fibrillation, which may influence the choice of BTK inhibitor treatment by prescribers. Further studies are needed to inform on optimal treatment sequencing of zanubrutinib and its combination with other agents. Here, we summarize existing clinical evidence for its efficacy and safety in mantle cell lymphoma, Waldenström macroglobulinemia, marginal zone lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and other B-lymphoproliferative indications. Plain Language Summary: Zanubrutinib is a drug that was shown to effectively treat cancer of B cells without causing excessive serious side effects Patients with certain B-cell malignancies (cancers of white blood cells) benefit from treatment with Bruton tyrosine kinase (BTK) inhibitors, drugs that block the BTK protein and keep cancer from growing and spreading. Patients experience extended survival with ibrutinib, the first-generation BTK inhibitor approved by US Food and Drug Administration (FDA); however, one in five patients quit treatment because of harmful side effects. Ibrutinib-related side effects such as increased risk of bleeding, atrial fibrillation (abnormal heart rhythm), and high blood pressure are thought to be caused by ibrutinib blocking other proteins besides the intended target protein BTK. To reduce these side effects, zanubrutinib, a next-generation BTK inhibitor, was designed to block BTK more specifically than ibrutinib. Results of clinical studies on zanubrutinib treatment appear promising in patients with several types of B-cell malignancies, including mantle cell lymphoma (MCL), Waldenström macroglobulinemia (WM), marginal zone lymphoma (MZL), chronic lymphocytic leukemia, and small lymphocytic lymphoma. There are not yet enough clinical data to determine which BTK inhibitor is most effective in treating B-cell malignancies without causing harmful side effects. Early data from the phase 3 ALPINE clinical study suggest that zanubrutinib works better than ibrutinib, and fewer patients experience side effects and quit treatment. Zanubrutinib is currently approved for use for treatment of adult patients with MCL who have received at least one prior therapy, for adults with WM, and for adults with MZL who have received at least one anti-CD20–based therapy.
AB - The availability of Bruton tyrosine kinase (BTK) inhibitors has brought about a paradigm shift in the treatment of patients with B-cell lymphomas and chronic lymphocytic leukemia. BTK was clinically validated as a target by the efficacy of the first-in-class inhibitor ibrutinib. The extended survival conferred by BTK inhibitors has brought long-term tolerability to the foreground. To minimize toxicities thought to be attributable to off-target kinase inhibition, a next generation of BTK inhibitors with greater selectivity was developed. In the United States, zanubrutinib, a next-generation BTK inhibitor, has been approved for treating adults with mantle cell lymphoma who have received at least one prior therapy, for adults with Waldenström macroglobulinemia, and for adults with relapsed or refractory marginal zone lymphoma who have received at least one anti-CD20–based therapy. Because few head-to-head comparative trials of BTK inhibitors have so far been reported, no BTK ‘inhibitor of choice’ can be identified. Zanubrutinib has promising efficacy in its approved indications and appears to have reduced cardiac toxicities, particularly atrial fibrillation, which may influence the choice of BTK inhibitor treatment by prescribers. Further studies are needed to inform on optimal treatment sequencing of zanubrutinib and its combination with other agents. Here, we summarize existing clinical evidence for its efficacy and safety in mantle cell lymphoma, Waldenström macroglobulinemia, marginal zone lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and other B-lymphoproliferative indications. Plain Language Summary: Zanubrutinib is a drug that was shown to effectively treat cancer of B cells without causing excessive serious side effects Patients with certain B-cell malignancies (cancers of white blood cells) benefit from treatment with Bruton tyrosine kinase (BTK) inhibitors, drugs that block the BTK protein and keep cancer from growing and spreading. Patients experience extended survival with ibrutinib, the first-generation BTK inhibitor approved by US Food and Drug Administration (FDA); however, one in five patients quit treatment because of harmful side effects. Ibrutinib-related side effects such as increased risk of bleeding, atrial fibrillation (abnormal heart rhythm), and high blood pressure are thought to be caused by ibrutinib blocking other proteins besides the intended target protein BTK. To reduce these side effects, zanubrutinib, a next-generation BTK inhibitor, was designed to block BTK more specifically than ibrutinib. Results of clinical studies on zanubrutinib treatment appear promising in patients with several types of B-cell malignancies, including mantle cell lymphoma (MCL), Waldenström macroglobulinemia (WM), marginal zone lymphoma (MZL), chronic lymphocytic leukemia, and small lymphocytic lymphoma. There are not yet enough clinical data to determine which BTK inhibitor is most effective in treating B-cell malignancies without causing harmful side effects. Early data from the phase 3 ALPINE clinical study suggest that zanubrutinib works better than ibrutinib, and fewer patients experience side effects and quit treatment. Zanubrutinib is currently approved for use for treatment of adult patients with MCL who have received at least one prior therapy, for adults with WM, and for adults with MZL who have received at least one anti-CD20–based therapy.
KW - B-cell malignancies
KW - Bruton tyrosine kinase
KW - BTK inhibitor
KW - chronic lymphocytic leukemia
KW - mantle cell lymphoma
KW - marginal zone lymphoma
KW - Waldenström macroglobulinemia
KW - zanubrutinib
UR - http://www.scopus.com/inward/record.url?scp=85131172088&partnerID=8YFLogxK
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U2 - 10.1177/20406207221093980
DO - 10.1177/20406207221093980
M3 - Review article
C2 - 35651781
AN - SCOPUS:85131172088
SN - 2040-6207
VL - 13
JO - Therapeutic Advances in Hematology
JF - Therapeutic Advances in Hematology
ER -