CD19-directed chimeric antigen receptor-modified T cells (CAR T) induce long-term remissions in 30–40% of relapsed/refractory large B-cell lymphomas. T-cell depletion and/or an immunosuppressive tumor microenvironment may lead to CAR T-cell failure. Pembrolizumab, an anti-PD1 immune checkpoint inhibitor, may cure T-cell fatigue after CAR T-cell treatment. For a study, researchers gave pembrolizumab 200 mg IV every 3 weeks to 12 patients with B-cell lymphomas who were either resistant to (n=9) or relapsed following (n=3) CD19-directed CAR T-cell (4-1BB–costimulated) treatment. The median period from CAR T-cell infusion to first pembrolizumab dosage was 3.3 months (range, 0.4-42.8 months). Pembrolizumab was well tolerated, with neutropenia (n=3; 25%) being the sole grade 3 adverse event.
After pembrolizumab, the best overall response rate was 25%. From (3 of 12 patients; 1 complete response; 2 partial responses). Just 1 patient (8%) had a stable illness, resulting in clinical benefit for 4 of 12 (33%) patients. Following pembrolizumab, 4 patients with clinical benefit reported a rise in the proportion of CAR T cells measured by mass cytometry by time of flight (CyTOF); 3 of these 4 patients also had increases in CAR19 transgene levels measured by quantitative polymerase chain reaction. In clinical responders, deep immune profiling utilizing CyTOF demonstrated greater CAR T-cell activation and proliferation as well as less T-cell fatigue. PD1 blocking with pembrolizumab following CD19-directed CAR T-cell treatment was safe and generated therapeutic responses in certain patients with B-cell lymphomas that are unresponsive to or have relapsed after CAR T-cell therapy.
