Patients with diffuse large B-cell lymphoma (DLBCL) who have not responded to available therapies, with relapsed or primary resistant disease, have a poor prognosis.
A single-center phase 2a study of the chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel showed efficacy against B-cell lymphomas. The JULIET phase 2 clinical trial evaluated the efficacy and safety of the CAR T-cell therapy tisagenlecleucel in adults with relapsed or refractory DLBCL (Schuster SJ, et al. N Engl J Med. 2019;380:45-56).
JULIET was a single-group, open-label, multicenter, international study of adults with relapsed or refractory DLBCL who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplant. At the March 8, 2017, data cutoff, 165 patients were enrolled, 111 of whom had a single dose of tisagenlecleucel. A total of 92% of patients also received bridging therapy. Before infusion, the patients underwent restaging, and 93% received lymphodepleting chemotherapy. The primary end point was best overall response rate (ORR; defined as combined percentage of patients who had a complete or partial response).
Among the 93 patients who had ≥3 months of follow-up or had discontinued the study before 3 months, the best ORR was 52%, including a complete response rate of 40% and a partial response rate of 12%. The rate of ORR and complete response was 38% and 32%, respectively, at 3 months, and 33% and 29%, respectively, at 6 months. The response rates were consistent across prognostic subgroups.
The median duration of response had not been reached; however, 79% of patients who had a complete response and 65% of all patients who had a response were projected to remain relapse-free at 12 months after having a response.
The most common grade 3 or 4 adverse events of special interest included cytokine release syndrome (22%), neurologic events (12%), cytopenia lasting more than 28 days (32%), infections (20%), and febrile neutropenia (14%). There were no deaths from tisagenlecleucel, cytokine release syndrome, or cerebral edema.
“Patients with relapsed or refractory DLBCL who are not eligible for high-dose therapy and hematopoietic-cell transplantation or for whom such therapy was not successful have very few treatment options,” concluded the researchers. “For these patients, tisagenlecleucel shows promise that will need to be confirmed through larger studies with longer follow-up.”