Single-center dose-finding phase 1 study of CD22-directed CAR T-cell therapy for large B-cell lymphomas progressing after CD19-directed CAR T-cell therapy

Outcomes are poor for patients with large B-cell lymphoma (LBCL) who relapse after CD19-directed CAR T-cell therapy. CD22 is a nearly universally expressed B-cell surface antigen. A phase 1 dose-finding study at Stanford University evaluated CD22-directed CAR T-cell therapy in patients with LBCL progressing after CD19 directed CAR T-cell therapy. The median number of previous lines of therapy was 4 (range 3-8). The maximum tolerated dose was 1 million CAR T-cells per kg. Of 29 patients receiving the maximum tolerated dose, no patients developed a dose-limiting toxicity or grade 3 or higher cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. Partial and complete responses were seen in 68% and 53% of patients, respectively. The authors conclude that the trial identified CD22 as in immunotherapeutic target in LBCL, and demonstrated tolerability and efficacy of CD22-directed CAR T-cell therapy in patients with progressive disease after CD19-directed CAR T-cell therapy.