tisagenlecleucel + pembrolizumab

tisagenlecleucel + pembrolizumab is an experimental combination therapy consisting of two immune-oncology drugs: tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy targeting CD19, and pembrolizumab, a monoclonal antibody inhibitor of programmed cell death protein 1 (PD-1). Tisagenlecleucel is indicated for relapsed/refractory (r/r) B-cell malignancies and works by engineering patient T cells to recognize and kill CD19-positive malignant B cells. Pembrolizumab inhibits PD-1, thereby blocking immune checkpoint signaling and enhancing T-cell mediated anti-tumor activity. This combination was studied to improve outcomes in r/r diffuse large B-cell lymphoma (DLBCL), aiming to overcome CAR-T cell exhaustion mediated by the PD-1/PD-L1 pathway. In the phase 1b PORTIA trial, this combination was feasible with a manageable safety profile; however, the trial was terminated early due to limited data and evolving treatment landscapes.