A new study supports the safety of salvage therapy with the anti-programmed cell death protein 1 (PD1) immune checkpoint inhibitor pembrolizumab after CD19-directed chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
The study, led by Ana África Martín López of the Hospital Universitario de Salamanca in Spain, was presented during the European Society for Blood and Marrow Transplantation-European Hematology Association Fifth European CAR T-cell Meeting.
Since only approximately 30%-40% of patients with R/R DLBCL achieve durable remissions, many patients will require subsequent treatments, the researchers noted, which is why pembrolizumab is sometimes administered with the hope that it will reverse T-cell exhaustion following CAR T-cell therapy.
The study included 59 patients with R/R DLBCL who received commercial CAR-T cell therapy at the Hospital Universitario de Salamanca between May 2019 and December 2022. Among the patients, 61% (n=36/59) received axicabtagene ciloleucel and 39% (n=23/59) received tisagenlecleucel.
Among the 59 patients treated with commercial CAR T-cell therapy, 31 (52.5%) experienced relapse or disease progression after the CAR-T treatment. Of the 31 patients who experienced relapse or progression, 17 received intravenous pembrolizumab 200 mg every three weeks as salvage therapy.
The median time from CAR T-cell infusion to the first pembrolizumab treatment was 42 days (range, 16-211) and with a median of two doses administered (range, 1-22).
The results showed pembrolizumab was well tolerated, with the only treatment-related adverse effects being immune effector cell-associated neurotoxicity syndrome (ICANS) grade 2 (n=1), neutropenia (n=7; 41.2%), and arthritis (n=1). The patient who developed ICANS after pembrolizumab received it only 16 days after infusion due to the rapid progression of the disease.
The best overall response rate after pembrolizumab was 23.5% (n=4), with all four of those patients achieving a complete response (23.5%).
“PD1 blockade with pembrolizumab after CD19-directed CAR T-cell therapy appears to be safe,” the researchers concluded. “Although some patients with R/R DLBCL who experienced disease relapse or progression after CAR-T may achieve clinical responses, it would be of interest to identify predictors of response together with developing more effective salvage therapy options.”
Martín López AA, Pérez López E, Cabero Martínez A, et al. Pembrolizumab after CAR T-cell therapy: a single center experience. Presented at the European Society for Blood and Marrow Transplantation-European Hematology Association Fifth European CAR-T cell Meeting; February 9-11, 2023; Rotterdam, Netherlands.