Bing-Neel syndrome: A case reports

Introduction Bing-Neel syndrome (BNS) is a rare complication of of Waldenström macroglobulinemia (WM) identified by involvement of central nervous system (CNS) lymphoplasmacytic cells. Case report We present a patient who was diagnosed with Bing-Neel syndrome four years after the diagnosis of Waldenström macroglobulinemia. Management & outcome The patient was admitted with neurological symptoms. There were lesions associated with WM involvement on brain imaging. The diagnosis was made by brain biopsy. High dose methotrexate treatment was given. Discussion CNS infiltrating agents such as fludarabine, methotrexate and cytarabine are often used in BNS treatment. Ibrutinib, which is a new bruton tyrosine kinase inhibitor, has recently started to be used in BNS treatment, as it has been shown to be effective and penetrate the CNS.

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Ibrutinib for the treatment of Bing-Neel syndrome, a complication of Waldenström macroglobulinemia: Patient case report

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155219830162 ◽

2019 ◽

Vol 25 (6) ◽

pp. 1534-1539 ◽

Cited By ~ 1

Author(s):

Lauren Hartsell ◽

Amanda Janes ◽

Chris Larck ◽

Steven Park ◽

Justin R Arnall

Keyword(s):

Case Report ◽

Kinase Inhibitor ◽

Rare Complication ◽

Treatment Strategies ◽

Treatment Modalities ◽

High Dose ◽

Waldenström Macroglobulinemia ◽

Multiple Treatment ◽

Waldenstrom Macroglobulinemia ◽

Dosing Strategy

Bing-Neel syndrome is a rare complication of Waldenström macroglobulinemia, characterized by infiltration of lymphoplasmacytic cells to the central nervous system. Multiple treatment modalities exist including purine analogs, bendamustine, high-dose methotrexate, or high-dose cytarabine. Of interest, ibrutinib, a Bruton tyrosine kinase inhibitor has also displayed efficacy in Bing-Neel syndrome. Current literature is limited for the treatment of Bing-Neel syndrome considering its rarity, and while ibrutinib is indicated for the treatment of Waldenström macroglobulinemia, it is utilized off-label for treatment of Bing-Neel syndrome. Additionally, debate exists regarding the recommended dosing strategy for ibrutinib for this indication with disease remission demonstrated at 560 mg and 420 mg. We present a case report that provides additional evidence for this debate with a patient who received 560 mg of ibrutinib initially and maintained disease control despite a dose reduction to 420 mg for tolerability. Ultimately, more data are needed to develop standardized Bing-Neel syndrome treatment strategies with specific consideration to the use of ibrutinib in this condition.

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A Case of Bing–Neel Syndrome Successfully Treated with Ibrutinib

Case Reports in Hematology ◽

10.1155/2018/8573105 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Daniel S. O’Neil ◽

Mark A. Francescone ◽

Karen Khan ◽

Alobeid Bachir ◽

Owen A. O’Connor ◽

...

Keyword(s):

Cell Lymphoma ◽

B Cell Lymphoma ◽

High Dose ◽

Lambda Light Chain ◽

Waldenström Macroglobulinemia ◽

Dose Methotrexate ◽

Nerve Sheath ◽

Waldenstrom Macroglobulinemia ◽

Rare Manifestation ◽

The Central Nervous System

Bing–Neel syndrome is a rare manifestation of Waldenström macroglobulinemia characterized by lymphoplasmacytic cells’ infiltration into the central nervous system. We present a case of a 74-year-old patient with a known diagnosis of Waldenström macroglobulinemia and newly depressed consciousness. Flow cytology of his cerebral spinal fluid demonstrated a lambda light chain-restricted population of B-cells consistent with a CD5+ CD10+ B-cell lymphoma. Magnetic resonance imaging suggested involvement of the left optic nerve sheath and the bilateral orbital and parietal parenchyma and leptomeninges. He was diagnosed with Bing–Neel syndrome and treated with intrathecal liposomal cytarabine, intravenous high-dose methotrexate, and rituximab without improvement. Subsequently, he started treatment with ibrutinib 560 mg daily and concurrent rituximab. Within three months, he showed clinical and radiologic improvement. The patient has continued on ibrutinib and has now been stable for over 36 months. This represents the longest reported period of successful treatment of Bing–Neel syndrome with ibrutinib.

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Central Nervous System Involvement by Waldenstrom Macroglobulinemia: A Case Report of the Bing–Neel Syndrome

Case Reports in Hematology ◽

10.1155/2019/4075960 ◽

2019 ◽

Vol 2019 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Ananth Arjunan ◽

Hema Rai

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Standard Dose ◽

Rare Complication ◽

Central Nervous System Involvement ◽

Serum Markers ◽

High Dose ◽

Neurologic Symptoms ◽

Waldenström Macroglobulinemia ◽

Waldenstrom Macroglobulinemia

Bing–Neel syndrome (BNS) is a rare complication of Waldenstrom macroglobulinemia (WM) defined by a lymphoplasmacytic infiltration of the central nervous system (CNS). Patients present with a range of neurologic symptoms of variable severity. Diagnosis requires a low threshold of suspicion and is considered in WM patients with unexplained neurologic symptoms. It can occur in the presence of quiescent serum markers of WM. Direct CNS tissue biopsy should be pursued if feasible and remains the gold standard for diagnosis. No standard of care treatment exists, but expert guidelines suggest intravenous chemotherapy in standard dose or high-dose regimens or use of oral ibrutinib. Consideration is also made for intravenous rituximab, intrathecal therapies, and autologous stem cell transplantation. Patient factors and tolerability should drive decisions regarding treatment choice in this arena, given a lack of data for standard frontline therapy.

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Bruton tyrosine-kinase inhibitor on the rise: acalabrutinib in Waldenström macroglobulinemia

The Lancet Haematology ◽

10.1016/s2352-3026(19)30214-5 ◽

2020 ◽

Vol 7 (2) ◽

pp. e85-e86

Author(s):

Christian Buske

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitor ◽

Kinase Inhibitor ◽

Waldenström Macroglobulinemia ◽

Waldenstrom Macroglobulinemia ◽

Bruton Tyrosine Kinase

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A Phase II Trial of the Bruton Tyrosine-Kinase Inhibitor Zanubrutinib (BGB-3111) in Patients with Relapsed/Refractory Waldenström Macroglobulinemia

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-21-0539 ◽

2021 ◽

pp. clincanres.0539.2021

Author(s):

Gang An ◽

Daobin Zhou ◽

Shu Cheng ◽

Ke-Shu Zhou ◽

Jianyong Li ◽

...

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitor ◽

Phase Ii ◽

Kinase Inhibitor ◽

Phase Ii Trial ◽

Waldenström Macroglobulinemia ◽

Waldenstrom Macroglobulinemia ◽

Bruton Tyrosine Kinase

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Ibrutinib in primary central nervous system diffuse large B-cell lymphoma

CNS Oncology ◽

10.2217/cns-2019-0022 ◽

2020 ◽

Vol 9 (1) ◽

pp. CNS51 ◽

Cited By ~ 1

Author(s):

Justin T Low ◽

Katherine B Peters

Keyword(s):

Kinase Inhibitor ◽

Cell Lymphoma ◽

Primary Cns Lymphoma ◽

B Cell Lymphoma ◽

Cns Lymphoma ◽

High Dose ◽

Standard Regimen ◽

Large B Cell Lymphoma ◽

Dose Methotrexate ◽

Bruton Tyrosine Kinase

The standard regimen for the treatment of newly diagnosed primary CNS lymphoma (PCNSL) remains regimens that contain high-dose methotrexate (MTX). While these regimens can provide control for some patients, there is a dearth of options for the treatment of patients with PCNSL who cannot tolerate MTX-containing regimens, or whose cancers are refractory to MTX. In this article, we review a promising new option; ibrutinib, a Bruton tyrosine kinase inhibitor, for patients with relapsed and refractory PCNSL.

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Ibrutinib effect in acquired von Willebrand syndrome secondary to Waldenström macroglobulinemia

Therapeutic Advances in Hematology ◽

10.1177/20406207211039326 ◽

2021 ◽

Vol 12 ◽

pp. 204062072110393

Author(s):

María Poza ◽

Rodrigo Íñiguez ◽

Irene Zamanillo ◽

Sara Redondo ◽

Rafael Alonso ◽

...

Keyword(s):

Von Willebrand Factor ◽

Kinase Inhibitor ◽

Receptor Expression ◽

Acquired Von Willebrand Syndrome ◽

Waldenström Macroglobulinemia ◽

Risk Of Bleeding ◽

Waldenstrom Macroglobulinemia ◽

Bruton Tyrosine Kinase ◽

Von Willebrand ◽

Willebrand Factor

The pathological increase of clonal IgM in Waldenström macroglobulinemia can be associated with acquired von Willebrand syndrome and can be a major risk of bleeding symptoms in this subgroup of patients with Waldenström macroglobulinemia. The Bruton tyrosine kinase inhibitor ibrutinib is one of the approved treatments for symptomatic Waldenström macroglobulinemia. However, some controversy exists regarding the use of ibrutinib in these patients with high risk of bleeding because of its antiaggregant effect that could increase the risk of bleeding. Here, we present the case of a patient with Waldenström macroglobulinemia with associated acquired von Willebrand syndrome and progressively significant bleeding symptoms, who experienced a rapid increase in von Willebrand factor with ibrutinib treatment, despite only reaching a partial response in IgM levels similar to those reached with other previous treatments. We suggest that the control over the monoclonal protein is not the only mechanism that explains the good response, improvement in the bleeding symptoms and von Willebrand factor levels. This fact could be explained by the reduced glycoprotein Ib receptor expression induced by ibrutinib and the consequent von Willebrand factor increase in peripheral blood.

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Ibrutinib in the management of Waldenstrom macroglobulinemia

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155218786037 ◽

2018 ◽

Vol 25 (2) ◽

pp. 434-441 ◽

Cited By ~ 1

Author(s):

Amir Yosef ◽

Emily Z Touloukian ◽

Vinod E Nambudiri

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Kinase Inhibitors ◽

Kinase Inhibitor ◽

Critical Role ◽

Pharmacy Practice ◽

Progression Free Survival ◽

Waldenström Macroglobulinemia ◽

Waldenstrom Macroglobulinemia ◽

Bruton Tyrosine Kinase

Bruton tyrosine kinase plays a critical role in hastening cell proliferation. Bruton tyrosine kinase inhibitors are a class of immunotheraputic agents that disrupt this signaling pathway. Ibrutinib, a novel Bruton tyrosine kinase inhibitor approved by the Food and Drug Administration (FDA) for the treatment of Waldenstrom macroglobulinemia in patients who have failed treatment with other agents, has emerged as an important therapeutic agent in the management of Waldenstrom macroglobulinemia and other plasma cell dyscrasias. Ibrutinib has shown to increase progression free survival and improve overall mortality. We present a review of ibrutinib, beginning with an overview of the Bruton tyrosine kinase pathway and clinically relevant gene mutations impacting treatment and prognosis for patients with Waldenstrom macroglobulinemia, followed by evidence supporting therapeutic indications for ibrutinib, and detailing its safety and efficacy evidence, current clinical guidelines, adverse effects and their management, and finally challenges of drug resistance. We also present findings on newly developed Bruton tyrosine kinase inhibitors in the therapeutic pipeline to provide readers insight into this rapidly evolving corner of oncology pharmacy practice.

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