Tisagenlecleucel Leads to High Rates of Durable Response in Relapsed, Refractory DLBCL

January/February 2019, Vol 12, Special Issue: Payers’ Perspectives in Oncology: ASH 2018 Highlights

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.”

Last modified: February 27, 2019
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