Case Report: Secondary neurolymphomatosis successfully treated with sequential Bruton’s tyrosine kinase inhibitor and bispecific antibody therapy

Background Neurolymphomatosis frequently impairs physical function, rendering patients unable to tolerate chimeric antigen receptor T-cell therapy (CAR-T). An alternative treatment strategy which can cross the blood-nerve barrier is warranted. Case A 64-year-old woman had a history of MYD88L265P mutated diffuse large B-cell lymphoma (DLBCL) successfully treated with Pola-R-CHP plus high-dose methotrexate one year prior. However, she developed progressive muscle weakness in her limbs, with a three-month history. Upon admission, she was bedridden, unable to resist gravity, and experienced bladder and rectal disturbances. Imaging studies revealed neurolymphomatosis involving the bilateral trigeminal nerves, cervical/brachial plexus, brachial nerves, lumbosacral plexus, and femoral nerves. Ibrutinib 560 mg/day combined with rituximab led to complete remission, and she regained the ability to walk within three months. Unfortunately, neurolymphomatosis relapsed after six months of ibrutinib treatment. Epcoritamab led to another complete remission, with a progression-free survival of six months. The adverse events were manageable, including Grade 1 cytokine release syndrome. Conclusion This report is the first to demonstrate the effectiveness of epcoritamab in treating neurolymphomatosis. Bispecific antibodies may serve as a valuable bridging therapy for CAR-T, helping to restore their physical function. Bruton’s tyrosine kinase inhibitors could also be an option for MYD88L265P mutated disease.