teniposide + PD-1 monoclonal antibody + selinexor

The VPX regimen is an investigational combination therapy consisting of teniposide, a PD-1 monoclonal antibody, and selinexor, currently being evaluated for the treatment of relapsed or refractory primary central nervous system lymphoma (PCNSL). Teniposide is a podophyllotoxin derivative that acts as a topoisomerase II inhibitor, capable of crossing the blood-brain barrier to exert cytotoxic effects by inducing DNA strand breaks. Selinexor is a first-in-class selective inhibitor of nuclear export (SINE) that binds to and inhibits exportin 1 (XPO1), leading to the nuclear accumulation and activation of tumor suppressor proteins and the downregulation of oncogenic mRNAs. The PD-1 monoclonal antibody component serves as an immune checkpoint inhibitor, enhancing T-cell mediated anti-tumor responses by blocking the PD-1/PD-L1 signaling axis. This combination is being studied by The First Affiliated Hospital of Soochow University to leverage synergistic cytotoxic and immunomodulatory mechanisms in aggressive CNS lymphomas.