复发性原发性中枢神经系统淋巴瘤的治疗选择

Primary CNS lymphoma (PCNSL) constitutes a rare extranodal variant of non-Hodgkin lymphoma (NHL) with an annual incidence of 0. 45/100,000. Given the paucity of large prospective clinical trials, there is no consensus treatment for refractory or relapsed (r/r) PCNSL, and available strategies are largely based on retrospective analyses. Patient age, performance status, previously administered treatment, duration of response, and molecular characteristics guide selection of salvage therapy. Patients with a good performance status (KPS >70), particularly 65 years, and adequate organ function should be considered for salvage polychemotherapy. Based on its high overall response rate even in the relapsed setting, we choose high-dose ( 3. 5g/m 2 ) methotrexate (HD-MTX) based regimens, e. g. , R-MPV (rituximab, HD-MTX, procarbazine, and vincristine), for remission re-induction as long as patients were sensitive to first line HD-MTX-based regimens, especially when duration of previous response was 1 year.

Following successful remission induction, we choose myeloablative chemotherapy (e. g. , thiotepa, busulfan, cyclophosphamide) and subsequent autologous stem cell transplant in curative intent whenever feasible. Alternatively, conventional chemotherapy regimens (for example, monthly HD-MTX) or low-dose whole-brain radiation therapy (WBRT) are selected for consolidation in non-transplant candidates in complete remission.

In cases of HD-MTX refractory disease or contraindications, we use pemetrexed; temozolomide/rituximab; high-dose cytarabine; or whole brain radiation for remission induction. Clinical trial participation is considered as well. Emerging therapies for upfront or salvage therapy under ongoing investigation include bruton tyrosine kinase inhibition (e. g. , ibrutinib), immunomodulatory drugs (e. g. , lenalidomide), immune checkpoint inhibitors (ICI, e. g. , nivolumab), and chimeric antigen receptor T (CAR-T) cell therapy.