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

Abstract

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.

Bing-Neel Syndrome, a Rare Presentation of Waldenström Macroglobulinemia—A Multicenter Report by the Polish Lymphoma Research Group

“…Two patients were treated with ibrutinib in the first line and one in the salvage setting. Alike methotrexate and cytarabine, ibrutinib is also known to pass the blood-brain barrier [ 15 , 16 , 17 , 18 , 19 ]. As was shown by Castillo et al ibrutinib given at a daily dose of 420 or 560 mg daily is very effective in the treatment of BNS, with 85% of patients having improvement or resolution of BNS symptoms, 83% having improvement or resolution of radiologic abnormalities, and 47% having a clearance of the disease in the CSF at the best response [ 10 ].…”

Current and Emerging Treatments for Waldenström Macroglobulinemia

“…Ibrutinib is an oral agent that is a potent irreversible inhibitor of BTK and is highly effective, with the best treatment responses observed in patients with MYD88 L265P and CXCR4 WT mutations [51, 52]. Ibrutinib also can cross the blood-brain barrier and may be effective for Bing-Neel syndrome, a rare complication of WM [53]. However, ibrutinib is not specific and blocks several other kinases.…”