Longer term analyses of Kymriah-JULIET study for DLBCL.- Novartis

Novartis announced longer-term analyses of both ELIANA and JULIET, the pivotal clinical trials of Kymriah (tisagenlecleucel) in children and young adult patients with relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) and adult patients with r/r diffuse large B-cell lymphoma (DLBCL), respectively. In these analyses, Kymriah continued to demonstrate strong efficacy with durable responses and maintained a consistent and well-characterized safety profile. These data are being presented at the 60th American Society of Hematology (ASH) annual meeting. Additionally,the New England Journal of Medicine published online the 14-month results from JULIET, the study led by the Abramson Cancer Center at the University of Pennsylvania.

The 19-month analysis from the JULIET study of Kymriah in adult patients with r/r DLBCL showed prolonged durability of response in patients (n=99) who had previously been through multiple rounds of chemotherapy and unsuccessful stem cell transplants. The overall response rate (ORR) after a median of 19 months of follow-up was 54% (95% CI, 43% - 64%; CR, 40%; partial response [PR], 13%) among patients who were followed for at least 3 months or discontinued earlier. The mDOR was not reached at the time of analysis indicating most responders were still experiencing a response at the time of analysis; and the relapse-free probability, which was 66% (95% CI, 51%-78%) at 6 months, remained consistent at 64% (95% CI, 48%-76%) between 12-month and 18-month analyses. Further, 54% (15/28) of patients who had achieved a PR converted to CR. Median OS for all infused patients was 11.1 months (95% CI, 6.6 months-NE) and not reached (95% CI, 21 months-NE) for patients in CR. The OS probability was 48% (95% CI, 38%-57%) at 12 months and 43% (95%CI, 33%-53%) at 18 months (max follow-up, 29 months). Analyses of ORR, DOR and OS data showed consistent results across all patient subgroups, regardless of relapsed/refractory status, age and high-risk cytogenetics.

The safety profile observed in the 19-month follow-up from JULIET continued to be consistent with previous reports and no deaths occurred due to causes other than disease progression in this longer-term follow up analysis. Within eight weeks of infusion with Kymriah, Grade 3/4 CRS, as defined by the Penn Grading Scale, was reported in 23% of patients. CRS management was conducted per the Penn CRS management algorithm, which is specific to Kymriah. Tocilizumab and steroids were used in 16% and 11% of patients, respectively, to treat CRS. Eleven percent of patients had Grade 3/4 neurologic adverse events, which were managed with supportive care. The updated JULIET data will be presented today in a poster at the ASH annual meeting (Abstract #1684; Saturday, December 1, 6:15 PM PST).

See - Schuster S., et al." Tisagenlecleucel in Adult Relapsed/Refractory Diffuse Large B-Cell Lymphoma". N Engl J Med. December 2018.