Fourteen months results from JULIET trial of Kymriah for patients with DLBCL.- Novartis

Novartis announced 14-month results from the pivotal JULIET clinical trial showing ongoing durable responses are achievable with Kymriah (tisagenlecleucel) when administered to adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL).

The overall response rate (ORR) was 52% (95% confidence interval [CI], 41% - 62%), among 93 evaluable patients who were followed for at least 3 months or discontinued earlier. A complete response (CR) was achieved in 40% of patients and 12% achieved a partial response (PR). Of the patients in CR at month 3, 83% remained in CR at month 12, and the median duration of response was not reached, indicating sustainability of response. These data will be presented in an oral presentation at the 23rd Annual Congress of the European Hematology Association (EHA) (Abstract # S799; Saturday, June 16, 11:30AM CEST).

In the JULIET study, the relapse-free probability at 12 months after a patient's first response (n=48) was 65% (95% CI, 49%-78%). In fact, 54% (13/24) of patients who had achieved a PR converted to CR, including two patients between months 9 and 12. Median overall survival (OS) was not reached for patients in CR (95% CI, 17.9-NE). The OS rate at 12 months was 49% and median OS was 11.7 months among all infused patients (n=111) (95% CI, 6.6-NE). The median time from infusion to data cutoff was 14 months with a maximum time from infusion of 23 months.

At the time of data cutoff, no patients in response following treatment with Kymriah proceeded to stem cell transplant. Within eight weeks of infusion with Kymriah, Grade 3/4 cytokine release syndrome (CRS), as defined by the Penn Grading Scale - a rigorous scale for grading CRS -, was reported in 22% of patients (14% grade 3; 8% grade 4). Fifteen percent of patients received tocilizumab for treatment of CRS, including only 3% of patients with Grade 2 CRS and 50% of patients with Grade 3 CRS. CRS is a known complication of CAR-T therapy that may occur when the engineered cells become activated in the patient's body. CRS was managed globally using prior site education on implementation of the CRS treatment algorithm. No deaths due to cerebral edema were reported. In this analysis, 12% of patients had grade 3/4 neurologic adverse events, which were managed with supportive care. Grade 3/4 cytopenias lasting more than 28 days, grade 3/4 infections and grade 3/4 febrile neutropenia occurred in 32%, 20% and 15% of patients, respectively.