|Anti-CD19 CAR T-cell therapy effective in adult relapsed or refractory DLBCL—a report of phase 2 study|
|Patients with diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin’s lymphoma, have a rate up to 50% of refraction or recurrence after first-line immunochemotherapy regimens containing rituximab (anti-CD20 antibodies). Among those with refractory or relapsed DLBCL, salvage chemotherapy followed by autologous bone-marrow transplantation is the standard second-line therapeutic strategy. However, more than 50% of patients suffer progression 3 years after transplantation. Tisagenlecleucel, anti-CD19 CAR T-cell, has been reported to be effective in children and young adults with recurrent or refractory acute lymphoblastic leukaemia accompanying with serious but reversible side effects, therefore tisagenlecleucel has been approved by the FDA for those patients. In a single-centre, phase 2a study, the response rate was 50% at 3 months among adult patients with relapsed or refractory DLBCL treated with tisagenlecleucel, indicating the value of further investigations. To further determine the efficacy and safety of tisagenlecleucel in adult patients with relapsed or refractory DLBCL, investigators conducted this single-arm, open-label, multi-centre, phase 2 study (the JULIET trial, here).
Patients with relapsed or refractory DLBCL, who were 18 years of age or older and had had previously at least two lines of therapy including rituximab and anthracycline were recruited in this study. The primary end point was the best overall response rate (complete response plus partial response). Secondary end points were composed of response duration, overall survival, safety, cellular kinetics, and evaluation of biomarkers. A total of 93 patients received an infusion of CAR T cells. The overall responses rate was 52%-- the complete response rate was 40%, whereas the partial response rate was 12%. At 12 months since the initial treatment response, the relapse-free survival rate was estimated to be 65%. No unknown adverse events related to treatment were observed. Three patients died with 30 days after infusion due to disease progression. No deaths resulted from tisagenlecleucel, cytokine release syndrome, or cerebral edema. It is worth noting that response rates were consistent across subgroups, which were unrelated to CD19 expression or immune checkpoint activation statues.
This trial indicates that anti-CD19 CAR T-cell therapy is effective in adult patients with recurrence or refraction. Further investigations involving larger cohorts are warranted to test the efficacy and safety of tisagenlecleucel as the third-line therapy in DLBCL patients.
This trial was supported by a pharmaceutical company.