Successful Management of a Patient with Refractory Primary Central Nervous System Lymphoma by Zanubrutinib

Abstract

Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal non-Hodgkin lymphoma, and the most frequent histological type is diffuse large B-cell lymphoma (DLBCL). Bruton's tyrosine kinase inhibitor (BTKi) has shown clinical activity in DLBCL. We herein report a 53-year-old man who presented with binocular diplopia, gait instability, dizziness and bucking. He was diagnosed with PCNSL by cranial magnetic resonance imaging (MRI) scan and brain biopsy. Next-generation sequencing (NGS) examination identified multiple genetic abnormalities. The patient was started on a high-dose methotrexate (HD-MTX)-based protocol for two courses. However, the patient developed disease progression. The patient's phenotypic and genetic characteristics strongly suggested BN2-DLBCL, and zanubrutinib was added to the subsequent chemotherapy regimen. The treatment was well tolerated, and complete remission (CR) was achieved after three courses of chemotherapy with the new regimen. The patient then received autologous hematopoietic stem cell transplantation after four courses of chemotherapy with the new regimen. MRI revealed stable CR. Here, we report a successful case of refractory PCNSL treated with zanubrutinib. Small molecules, such as zanubrutinib, may be selectively integrated into firstline regimens of PCNSL to enhance curative effect and reduce recurrence.

Case report: CD19-directed CAR-T cell therapy combined with BTK inhibitor and PD-1 antibody against secondary central nervous system lymphoma

“…Zanubrutinib has superior target effects by blocking several essential molecular pathways, including BCR signaling, BTK or B-lymphocyte kinase, Toll-like receptor (TLR) signaling and downregulating exhaustion markers, such as PD-1, TIM-3, and LAG-3 ( 30 ). Zanubrutinib could cross the BBB to exert its effect, alleviating Bing–Neel syndrome with CNS lymphoplasmacytic cell infiltration among Waldenström macroglobulinemia (WM) patients and successfully applied to refractory PCNSL case ( 32 , 33 ). Notably, emerging evidence has identified that zanubrutinib could modulate the immune system by inhibiting interleukin-2-inducible T-cell kinase (ITK) in T cells, which reduces T cell differentiation and shifting the balance of Th1/Th2 cells or enriches Th17 cell subsets.…”

Evidence-based expert consensus on the management of primary central nervous system lymphoma in China

“…As for two other BTKi currently available in China, 23 and 16 CNSL patients treated with orelabrutinib or zanubrutinib, respectively, were reported in a retrospective study, or in case series. The outcomes of these BTKi for PCNSL need to be followed-up [86][87][88].…”

Novel insights into the biomarkers and therapies for primary central nervous system lymphoma

“… 60 A successful case of refractory PCNSL treated with zanubrutinib has been reported. 61 The 53-year-old patient who developed progressive disease (PD) after two courses of HD-MTX-based regimen achieved CR after subsequent three courses of zanubrutinib plus chemotherapy. The patient received ASCT after four courses of zanubrutinib with chemotherapy, and his MRI revealed stable CR.…”