JULIET Trial: Tisagenlecleucel Sustains Disease Control in DLBCL

According to an update presented at the ASH annual meeting, tisagenlecleucel (Kymriah, Novartis) produced high response rates and durable responses in a cohort of heavily pretreated adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Tisagenlecleucel (Kymriah, Novartis) is a CD19‑directed genetically modified autologous T-cell immunotherapy indicated for the treatment of patients up to 25 years of age with B‑cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. It was evaluated via the JULIET trial (a single-arm, open-label, multicenter, global, phase II trial examining tisagenlecleucel in adult patients with clinically active relapsed/refractory DLBCL. Previously, JULIET had demonstrated that the treatment has a high rate of durable complete response and a manageable safety profile in that patient population.

By data cutoff, the study had enrolled 167 patients 18 years or older who had received two or more lines of therapy (including rituximab and an anthracycline) and were ineligible for or had failed autologous stem cell transplant (ASCT). Of those, 115 were infused with a single dose of tisagenlecleucel (99 considered to be in the main cohort). Subjects’ median age was 56 years (range, 22–76 years). At study entry, 77% of infused patients had stage III/IV disease. About half of patients had received three or more prior lines of antineoplastic therapy, and about half 49% had undergone a prior ASCT.

Median time from infusion to data cutoff was 19.3 months. Of the 99 patients in the main cohort, all were evaluable for efficacy. Objective response rate was 54%, complete response rate was 40%, and partial response rate was 13%. Median duration of response was not reached; but the researchers estimated that the probability of being relapse free was 66% at six months and 64% at 12 and 18 months. Furthermore, the study observed no relapses beyond 11 months post-infusion, and no patients proceeded to allogeneic SCT or ASCT while in remission.

The most common grade 3 or 4 adverse events were cytopenia lasting longer than 28 days (34%), cytokine release syndrome (23%), infections (19%), febrile neutropenia (15%), neurological events (11%), and tumor lysis syndrome (2%). Three patients died within 30 days of infusion due to disease progression, but no treatment-related mortality occurred.

The study authors, led by Stephen J. Schuster, MD, of the Lymphoma Program at Abramson Cancer Center, University of Pennsylvania, said that “efficacy was consistent in all predefined subgroups, including elderly patients, patients with relapsed/refractory disease, and other clinical or biological subgroups expected to have a worse prognosis with available treatments.”