Key Points
• Conclusions/Relevance: “Our data suggest that PD-1 blockade therapy can be active in patients with relapsed/refractory DLBCL after failure of CAR T cell therapy who had PD-L1 expression in tumor cells and high PD-1 level in tumor-infiltrated T cells.”
• The authors highlighted the unmet need for effective salvage treatments for patients with aggressive DLBCL who develop relapsed/refractory lymphoma following CART19 therapy.
• The researchers previously constituted tandem CART19/20 cells to enhance durable antitumor response, with patients exhibiting longer progression-free survival. A proportion of CART19/20-treated patients, however, progressed and needed salvage therapies. In the current study, the researchers assessed data from five patients with relapsed/refractory DLBCL whose disease progressed or relapsed following CART19/20 therapy. These patients were then administered salvage therapy in the form of PD-1-blocking antibodies as salvage therapy.
• In sum, 2 of 5 patients attained complete remission, with one remaining in remission for more than 21 months. Furthermore, 1 of 5 patients attained partial remission, and the last 2 patients experienced disease progression. Of note, no ≥ 3 grade toxicities or treatment-related deaths happened.
• Adaptive resistance to CART immunotherapy was influenced by the loss of tumor antigens and the emergence of an immunosuppressive tumor microenvironment. Tumor cells taken from all five patients expressed CD19 and CD20 both before and after failure of CART19/20 therapy. More CD3+ T cells in tumor microenvironment were observed at relapse.
• The authors wrote that “PD-L1 expression in tumor cells and high PD-1 level in T cells might be potential biomarkers to predict the outcome of anti-PD-1 antibodies in relapsed/refractory DLBCL and PD-1 blockade therapy is recommended for patients in this setting after failure of CART therapy.”