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Blood. 2017 Apr 20;129(16):2224-2232. doi: 10.1182/blood-2016-10-747345. Epub 2017 Feb 6.

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

Author information

Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Weill Department of Medicine, Weill Cornell Medical College, New York, NY.
David Geffen School of Medicine at UCLA, Los Angeles, CA.
Hemato-oncology Department, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris Diderot University, Sorbonne Paris-Cité, Paris, France.
Winship Cancer Institute of Emory University, Atlanta, GA.
Hematologie, Centre Hospitalier Universitaire, Université de Lille, Lille, France.
Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Clinical Research Alliance, Center for Lymphoma and Myeloma, Weill Cornell Medical College, New York, NY.
Florida Cancer Specialists, Atlantis, FL.
Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
Division of Hematology and Medical Oncology, Department of Medicine, Hofstra Northwell School of Medicine, Hempstead, NY.
Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA; and.
City of Hope National Medical Center, Duarte, CA.


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 as #NCT01980628.

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