Six-Month Analysis of CTL019 Demonstrates Sustained Responses in Refractory DLBCL Patients

December 11, 2017

A potentially practice-changing study presented at 2017 ASH shows high rates of sustained complete response in patients with relapsed/refractory diffuse large B-cell lymphoma who were treated with CTL019 CAR T-cell therapy.

CTL019 (tisagenlecleucel), an investigational chimeric antigen receptor (CAR) T-cell therapy that identifies and eliminates CD19-expressing B cells, appears to be highly effective in refractory lymphoma patients. Researchers reported the latest results from the JULIET trial (ClinicalTrials.gov identifier: NCT02445248) at the 2017 annual meeting of the American Society of Hematology (ASH), held December 9-12 in Atlanta, Georgia, demonstrating high rates of complete responses at 3 months being sustained at 6 months in a cohort of highly pretreated adult patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL).

The results confirmed earlier findings from an interim analysis. The updated analysis also demonstrated that centralized manufacturing was feasible in the first global study of CAR T-cell therapy in DLBCL. The researchers reported that cytokine release syndrome (CRS) and other adverse events (AEs) appeared to be effectively managed by appropriately trained investigators.

This current trial is a single-arm, open-label, multicenter, global, pivotal phase II trial of CTL019 in adults with r/r DLBCL. All the patients are 18 years or older with r/r DLBCL and have progressed after receiving two or more lines of chemotherapy. These patients also were ineligible for autologous stem cell transplant or had failed it.

Centrally manufactured CAR T-cells were provided to patients at 27 study centers in 10 countries on 4 continents. CTL019 was manufactured at two sites (United States and Germany). The latest interim analysis of the international JULIET trial showed that for 46 patients with at least 6 months of follow-up, the overall response rate was 37%, with 30% achieving a complete response and 7% achieving a partial response. Among 81 patients treated, those whose signs of cancer had gone away at 3 months remained relapse-free at 6 months and beyond.

Lead study author Stephen Schuster, MD, a professor of hematology/oncology at the Perelman School of Medicine at the University of Pennsylvania (Penn) and Penn's Abramson Cancer Center, said the investigators don’t completely understand why these remissions are so durable.  However, he said these findings are exciting and will change how this disease is managed when standard therapies fail.

Dr. Schuster said primary therapy will fail in about one-third of patients with DLBCL, and half of these patients will not be candidates for stem cell transplantation, which is considered the best second-line treatment approach.

Subgroup analyses showed no difference in outcomes based on prior DLBCL treatment or risk factors. Of the 81 patients included in JULIET, the responding patients continue to be followed without any additional therapy, and median durable overall response and overall survival have yet to be reached. Most of the AEs were seen shortly after infusion and included CRS and neurotoxicities. There were no deaths attributable to CTL019, CRS, or neurological events.

Dr. Schuster said several factors set this trial apart from other investigations of CAR T-cell therapies, including that the therapy was done on an outpatient basis for many patients (26%).