RESUMEN
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive lymphoma of the brain with poor prognosis. The scarcity of cell lines established using PCNSL makes it difficult to conduct preclinical studies on new drugs. We aimed to explore the effect of selinexor combined with zanubrutinib in PCNSL using established PCNSL cells and an orthotopic PCNSL model. Primary PCNSL cells were successfully cultured. Selinexor inhibited proliferation, induced G1 phase arrest, and promoted apoptosis, however, induced drug resistance in PCNSL. Selinexor combined with zanubrutinib had a synergistic effect on PCNSL and prevented the onset of selinexor resistance in PCNSL by inhibiting AKT signaling. Moreover, selinexor combined with zanubrutinib notably slowed tumor growth and prolonged survival compared to that of the control. Overall, the addition of zanubrutinib to selinexor monotreatment had a synergistic effect in vitro and prolonged survival in vivo.
RESUMEN
BACKGROUND: Leptomeningeal metastasis (LM) is a severe lung cancer complication, with potentially fatal consequences. The use of intrathecal therapy (IT) combined with systemic therapy has shown promise as a treatment approach for LM. Thus, this study aimed to evaluate the features and responses to IT combined therapy and identify determinants affecting patients with leptomeningeal metastasis resulting from lung adenocarcinoma (LM-LA). METHODS: A retrospective analysis of medical records from our hospital database was performed, covering from April 2018 to August 2022, for 37 patients diagnosed with LM-LA and treated with IT combined therapy. Patients who received IT combined therapy for LM-LA were evaluated for demographic characteristics, treatment efficacy, survival, and variables that impacted them. RESULTS: The median overall survival (mOS) of 37 patients was 16.0 months, and the survival rates at 6 and 12 months were 75.7% and 35.1%, respectively. Among the 21 patients with LM-LA who received IT combined with tyrosine kinase inhibitors (TKIs), the mOS was 17.0 months, which was significantly longer than that of patients treated with IT combined with chemotherapy (7.0 months, P = 0.010) and the best supportive care (6.0 months, P = 0.001). However, no significant survival benefit was observed in patients treated with IT combined with TKIs when compared with those treated with IT combined with PD-1 (5.0 months, P = 0.249). Multivariate analysis indicated that the combination of TKIs was an independent favorable prognostic factor for patients with LM-LA. CONCLUSION: Combination treatment is regarded as an additional option for patients with LM-LA. Compared with other combination therapies in our study, IT combined with TKI therapy provided a better survival outcome for patients with LM-LA.