CD19 CAR-T expressing PD-1/CD28 chimeric switch receptor as a salvage therapy for DLBCL patients treated with different CD19-directed CAR T-cell therapies

Abstract

CD19-targeted chimeric antigen receptor T (CAR T) cell therapy is a promising option to treat relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). However, the majority of CAR T-treated patients will eventually progress and require salvage treatment, for which there is no current standard. In this study, we analyzed data from 6 patients with R/R DLBCL who experienced progression following CD19-CAR T therapy, and then received CD19-specific CAR T cells that express a PD-1/CD28 chimeric switch-receptor (CD19-PD-1/CD28-CAR T) as salvage therapy at our institution. After the second infusion of CAR T cells, 3 of 6 patients achieved complete remissions and the duration of the response of responsive patients ranged from 8 to 25 months. One patient showed a stable disease. In contrast, 2/6 patients died on 60 days because of progression disease. Importantly, no severe neurologic toxicity or cytokine release syndrome was observed. These data suggest that CD19-PD-1/CD28-CAR-T cells, a novel anti-CD19 CAR-T cell therapy, elicit a potent and durable anticancer response, and can be used in the post-CD19-CAR T failure setting.

Keywords: CAR T cell therapy; DLBCL; PD-1/CD28 chimeric switch receptor; Salvage therapy.

Fig. 1

CD19-PD-1/CD28-CAR T induced durable clinical responses in R/R large B-cell lymphoma patients after failure of CD19-CAR T therapy. a Treatment response of each patient and the duration of response post-infusion with CD19-PD-1/CD28-CART. b Representative PET-CT scans at baseline and 90 days post first CAR-T infusion and salvage CAR T therapy. c The absolute number of CAR + peripheral blood mononuclear cells in patients who achieved clinical responses or non-responses were quantified by PCR