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      Call for Papers: Digital Diagnostic Techniques

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      About Pathobiology: 3.5 Impact Factor I 8.5 CiteScore I 1.088 Scimago Journal & Country Rank (SJR)

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      Bilateral Cystoid Macular Edema with Zanubrutinib Therapy: A Case Report

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          Abstract

          We present a patient with recurrent mantle cell lymphoma (MCL) who was treated with zanubrutinib, a Bruton’s tyrosine kinase inhibitor. He subsequently developed bilateral cystoid macular edema (CME) in both eyes. This is the first report of CME in a patient with MCL who was treated with zanubrutinib. CME was refractory to topical corticosteroid therapy, but sub-Tenon’s steroid injections and holding off zanubrutinib managed to decrease the CME. Treatment managed to prevent further vision loss but did not restore lost vision. The prompt ophthalmic exam is recommended for patients on zanubrutinib with decreased vision.

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          Role of Bruton’s tyrosine kinase in B cells and malignancies

          Simar Pal Singh, Floris Dammeijer, Rudi W. Hendriks (2018)
          Bruton’s tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role in oncogenic signaling that is critical for proliferation and survival of leukemic cells in many B cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) and is essential both for B cell development and function of mature B cells. Shortly after its discovery, BTK was placed in the signal transduction pathway downstream of the B cell antigen receptor (BCR). More recently, small-molecule inhibitors of this kinase have shown excellent anti-tumor activity, first in animal models and subsequently in clinical studies. In particular, the orally administered irreversible BTK inhibitor ibrutinib is associated with high response rates in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and mantle-cell lymphoma (MCL), including patients with high-risk genetic lesions. Because ibrutinib is generally well tolerated and shows durable single-agent efficacy, it was rapidly approved for first-line treatment of patients with CLL in 2016. To date, evidence is accumulating for efficacy of ibrutinib in various other B cell malignancies. BTK inhibition has molecular effects beyond its classic role in BCR signaling. These involve B cell-intrinsic signaling pathways central to cellular survival, proliferation or retention in supportive lymphoid niches. Moreover, BTK functions in several myeloid cell populations representing important components of the tumor microenvironment. As a result, there is currently a considerable interest in BTK inhibition as an anti-cancer therapy, not only in B cell malignancies but also in solid tumors. Efficacy of BTK inhibition as a single agent therapy is strong, but resistance may develop, fueling the development of combination therapies that improve clinical responses. In this review, we discuss the role of BTK in B cell differentiation and B cell malignancies and highlight the importance of BTK inhibition in cancer therapy.
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            Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma.

            Michael L Wang, Simon Rule, Peter George Martin … (2013)
            Bruton's tyrosine kinase (BTK) is a mediator of the B-cell-receptor signaling pathway implicated in the pathogenesis of B-cell cancers. In a phase 1 study, ibrutinib, a BTK inhibitor, showed antitumor activity in several types of non-Hodgkin's lymphoma, including mantle-cell lymphoma. In this phase 2 study, we investigated oral ibrutinib, at a daily dose of 560 mg, in 111 patients with relapsed or refractory mantle-cell lymphoma. Patients were enrolled into two groups: those who had previously received at least 2 cycles of bortezomib therapy and those who had received less than 2 complete cycles of bortezomib or had received no prior bortezomib therapy. The primary end point was the overall response rate. Secondary end points were duration of response, progression-free survival, overall survival, and safety. The median age was 68 years, and 86% of patients had intermediate-risk or high-risk mantle-cell lymphoma according to clinical prognostic factors. Patients had received a median of three prior therapies. The most common treatment-related adverse events were mild or moderate diarrhea, fatigue, and nausea. Grade 3 or higher hematologic events were infrequent and included neutropenia (in 16% of patients), thrombocytopenia (in 11%), and anemia (in 10%). A response rate of 68% (75 patients) was observed, with a complete response rate of 21% and a partial response rate of 47%; prior treatment with bortezomib had no effect on the response rate. With an estimated median follow-up of 15.3 months, the estimated median response duration was 17.5 months (95% confidence interval [CI], 15.8 to not reached), the estimated median progression-free survival was 13.9 months (95% CI, 7.0 to not reached), and the median overall survival was not reached. The estimated rate of overall survival was 58% at 18 months. Ibrutinib shows durable single-agent efficacy in relapsed or refractory mantle-cell lymphoma. (Funded by Pharmacyclics and others; ClinicalTrials.gov number, NCT01236391.)
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              Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia.

              John C. Byrd, Jennifer R. Brown, Susan O'Brien … (2014)
              In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton's tyrosine kinase, in patients at risk for a poor outcome. In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response rate as secondary end points. At a median follow-up of 9.4 months, ibrutinib significantly improved progression-free survival; the median duration was not reached in the ibrutinib group (with a rate of progression-free survival of 88% at 6 months), as compared with a median of 8.1 months in the ofatumumab group (hazard ratio for progression or death in the ibrutinib group, 0.22; P<0.001). Ibrutinib also significantly improved overall survival (hazard ratio for death, 0.43; P=0.005). At 12 months, the overall survival rate was 90% in the ibrutinib group and 81% in the ofatumumab group. The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group (42.6% vs. 4.1%, P<0.001). An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues. The most frequent nonhematologic adverse events were diarrhea, fatigue, pyrexia, and nausea in the ibrutinib group and fatigue, infusion-related reactions, and cough in the ofatumumab group. Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL. (Funded by Pharmacyclics and Janssen; RESONATE ClinicalTrials.gov number, NCT01578707.).
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                Author and article information

                Journal
                Journal ID (nlm-ta): Case Rep Oncol
                Journal ID (iso-abbrev): Case Rep Oncol
                Journal ID (hwp): CRO
                Journal ID (publisher-id): CRO
                Title: Case Reports in Oncology
                Publisher: S. Karger AG (Basel, Switzerland )
                ISSN (Electronic): 1662-6575
                Publication date (Electronic): 13 July 2023
                Publication date Collection: Jan-Dec 2023
                Publication date PMC-release: 13 July 2023
                Volume: 16
                Issue: 1
                Pages: 519-524
                Affiliations
                [1]Department of Ophthalmology, University of Kansas School of Medicine, Kansas City, KS, USA
                Author notes
                Correspondence to: Radwan Ajlan, rajlan@ 123456kumc.edu
                Article
                Publisher ID: 529069
                DOI: 10.1159/000529069
                PMC ID: 10359683
                PubMed ID: 37485014
                SO-VID: bc71b346-d187-4fd6-a56b-a5f0ed5727e2
                Copyright © © 2023 The Author(s). Published by S. Karger AG, Basel
                License:

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC) ( http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                Date received : 25 August 2022
                Date accepted : 4 January 2023
                Date: 2023
                Page count
                Figures: 1, References: 19, Pages: 6
                Funding
                No funding was used for this project.
                Categories
                Subject: Case Report

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: zanubrutinib,cystoid macular edema,mantle cell lymphoma,case report
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: zanubrutinib, cystoid macular edema, mantle cell lymphoma, case report

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