San Diego, California—Tisagenlecleucel, which has shown a high rate of durable complete response (CR) in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), demonstrated sustained activity in a long-term follow-up of the JULIET clinical trial, according to study data being presented at the 2018 ASH Annual Meeting.

Results from an updated analysis of the global JULIET trial will be presented by Richard T. Maziarz, MD, co-investigator in the study and Professor, Center for Hematologic Malignancies, Oregon Health & Science Knight Cancer Institute, Portland, Oregon.

According to Dr Maziarz and colleagues, the results account for a median of 19 months of follow-up, and demonstrate the sustained activity of tisagenlecleucel in these patients.

The single-arm, multi-center, open-label JULIET trial enrolled 167 patients aged ≥18 years with relapsed or refractory DLBCL who had received ≥2 previous lines of therapy that included rituximab and an anthracycline, and for whom autologous stem cell transplant (SCT) was not appropriate or effective.

The purpose of the study was to examine the effects of using tisagenlecleucel, a CD19-targeting chimeric antigen receptor T-cell therapy, in this patient population. The primary endpoint of the trial was overall response rate (ORR), determined by an independent review committee.

At the point of data cutoff, 115 of the enrolled patients received single-dose infusions of tisagenlecleucel; 90% received bridging therapy and 93% received lymphodepleting chemotherapy.

As of the interim analysis, the primary end point of ORR was met and achieved in approximately 60% of patients; 43% were complete responses and 16% were partial responses.

All 99 patients in the main cohort were followed-up with for 3 or more months or discontinued therapy and were evaluable for efficacy. The ORR in the updated analysis was 54%, with 40% CR and 13% partial response. According to Dr Maziarz and colleagues, the median duration of response was not reached.

They also stated that the probability of being relapse free at 6, 12, and 18 months was 66%, 64%, and 64%, respectively. There were no relapses observed beyond 11 months postinfusion.

The median overall survival (OS) for all infused patients was 11.1 months, and was not reached for patients with CRs. The probability of OS at 12 and 18 months was 48% and 43%, respectively. No patients proceeded to undergo allogeneic or autologous SCT during remission.

Notable grade 3 or 4 adverse events within 8 weeks of infusion included cytopenias lasting more than 28 days (34%), cytokine release syndrome (23%), infections (19%), febrile neutropenia (15%), neurological events (11%), and tumor lysis syndrome (2%).

A total of 3 patients died within 30 days of infusion because of disease progression; however, no deaths occurred from other causes during the follow-up analysis.

“Results from this longer-term follow-up show that tisagenlecleucel produced high response rates and durable responses in a cohort of heavily pretreated adult patients with r/r [relapsed or refractory] DLBCL,” Dr Maziarz and colleagues concluded.

“Efficacy was consistent in all predefined subgroups, including elderly patients, patients with r/r disease, and other clinical or biological subgroups expected to have a worse prognosis with available treatments, as demonstrated by similar and sustained DOR and OS following tisagenlecleucel treatment,” they added.—Janelle Bradley

Schuster SJ, Bishop MR, Tam C, et al. Sustained disease control for adult patients with relapsed or refractory diffuse large B-cell lymphoma: an updated analysis of Juliet, a global pivotal phase 2 trial of tisagenlecleucel. Presented at: the 60th ASH Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 1684.