Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma Journal Article


Authors: Noy, A.; de Vos, S.; Thieblemont, C.; Martin, P.; Flowers, C. R.; Morschhauser, F.; Collins, G. P.; Ma, S.; Coleman, M.; Peles, S.; Smith, S.; Barrientos, J. C.; Smith, A.; Munneke, B.; Dimery, I.; Beaupre, D. M.; Chen, R.
Article Title: Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma
Abstract: Marginal zone lymphoma (MZL) is a heterogeneous B-cell malignancy for which no standard treatment exists. MZL is frequently linked to chronic infection, which may induce B-cell receptor (BCR) signaling, resulting in aberrant B-cell survival and proliferation. We conducted a multicenter, open-label, phase 2 study to evaluate the efficacy and safety of ibrutinib in previously treated MZL. Patients with histologically confirmed MZL of all subtypes who received ≥1 prior therapy with an anti-CD20 antibody–containing regimen were treated with 560 mg ibrutinib orally once daily until progression or unacceptable toxicity. The primary end point was independent review committee–assessed overall response rate (ORR) by 2007 International Working Group criteria. Among 63 enrolled patients, median age was 66 years (range, 30-92). Median number of prior systemic therapies was 2 (range, 1-9), and 63% received ≥1 prior chemoimmunotherapy. In 60 evaluable patients, ORR was 48% (95% confidence interval [CI], 35-62). With median follow-up of 19.4 months, median duration of response was not reached (95% CI, 16.7 to not estimable), and median progression-free survival was 14.2 months (95% CI, 8.3 to not estimable). Grade ≥3 adverse events (AEs; >5%) included anemia, pneumonia, and fatigue. Serious AEs of any grade occurred in 44%, with grade 3-4 pneumonia being the most common (8%). Rates of discontinuation and dose reductions due to AEs were 17% and 10%, respectively. Single-agent ibrutinib induced durable responses with a favorable benefit–risk profile in patients with previously treated MZL, confirming the role of BCR signaling in this malignancy. As the only approved therapy, ibrutinib provides a treatment option without chemotherapy for MZL. This study is registered at www.clinicaltrials.gov as #NCT01980628. © 2017 by The American Society of Hematology.
Keywords: adult; aged; aged, 80 and over; disease-free survival; middle aged; clinical trial; fatigue; mortality; antineoplastic agents; disease free survival; antineoplastic agent; metabolism; phase 2 clinical trial; anemia; protein kinase inhibitor; drug administration schedule; recurrence; enzymology; pathology; protein tyrosine kinase; pyrimidines; b lymphocyte; b-lymphocytes; pneumonia; protein kinase inhibitors; immunology; immunotherapy; pyrazole derivative; multicenter study; pyrazoles; recurrent disease; protein-tyrosine kinases; drug administration; pyrimidine derivative; procedures; lymphoma, b-cell, marginal zone; drug effects; ibrutinib; very elderly; humans; human; male; female; antagonists and inhibitors; agammaglobulinaemia tyrosine kinase; chemically induced
Journal Title: Blood
Volume: 129
Issue: 16
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2017-04-20
Start Page: 2224
End Page: 2232
Language: English
DOI: 10.1182/blood-2016-10-747345
PUBMED: 28167659
PROVIDER: scopus
PMCID: PMC5399483
DOI/URL:
Notes: Article -- Export Date: 5 September 2017 -- Source: Scopus
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  1. Ariela Noy
    229 Noy