Case Report: Frontline CD19 CAR-T-cell therapy combined with targeted regimens induces durable complete remission in newly diagnosed secondary CNS lymphoma: a report of two cases

Abstract

Secondary central nervous system lymphoma (SCNSL) at initial diagnosis is an aggressive malignancy associated with a dismal prognosis. Standard-of-care treatments based on high-dose methotrexate often yield suboptimal outcomes. Although CD19-directed chimeric antigen receptor T-cell (CD19 CAR-T-cell) therapy is established in relapsed/refractory settings, its efficacy as a frontline intervention for SCNSL remains poorly defined. We report two cases of treatment-naive SCNSL that achieved sustained complete remission (CR) following a novel sequential therapeutic approach. Case 1 (65-year-old male) received Pola-ZR induction therapy (polatuzumab vedotin, zanubrutinib, and rituximab), while Case 2 (56-year-old female) received ZPR induction therapy (zanubrutinib, pomalidomide, and rituximab) followed by autologous stem cell transplantation. Both patients subsequently received CD19 CAR-T-cell infusions. Rapid CR was achieved and maintained for 24 and 21 months, respectively, with manageable toxicities. Frontline CAR-T-cell therapy combined with targeted agents may constitute a promising therapeutic paradigm for newly diagnosed SCNSL, yet these hypothesis-generating findings require validation in larger patient cohorts.