New CAR-T therapy data from ELIANA trial published.

Novartis announced updated results from the pivotal ELIANA clinical trial of Kymriah (tisagenlecleucel), formerly CTL019, in relapsed or refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL) have been published in The New England Journal of Medicine (NEJM).

New data include longer-term follow-up and efficacy in 75 infused patients, analysis of expansion and persistence of Kymriah, and longer-term safety. Kymriah became the first chimeric antigen receptor T (CAR-T) cell therapy to receive regulatory approval in August 2017, when it was approved by the FDA for the treatment of patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse, based on previous results from the ELIANA study, which was conducted in collaboration with the University of Pennsylvania (Penn) and Children's Hospital of Philadelphia (CHOP).

In the analysis of 75 infused patients with three or more months of follow-up, Kymriah demonstrated an overall remission rate of 81% (95% CI: 71% - 89%). Sixty percent of patients achieved complete remission (CR) and 21% of patients achieved CR with incomplete blood count recovery (CRi), with no minimal residual disease (MRD) detected among all responding patients (95% [58/61] by day 28). Median follow-up was 13.1 months.

Among patients who achieved CR/CRi, median duration of response was not reached. Remissions were durable with six-month relapse-free survival of 80%. Event-free survival was 73% at six months (95% CI: 60%-82%) and 50% at 12 months (95% CI: 35%-64%), with median event-free survival not reached. Overall survival in the 75 infused patients was 90% (95% CI: 81%-95%) at six months, and 76% (95% CI: 63%-86%) at 12 months. Kymriah was detected in patients up to 20 months. Median persistence of Kymriah was 168 days (range: 20-617; n=60 patients with CR/CRi) at data cutoff. All responding patients demonstrated B-cell aplasia (a low number of or absent B-cells), an on-target effect of treatment with Kymriah, and most received immunoglobulin replacement per local practice. Evaluable patients with a response at day 28 had a median time to maximum expansion of 10 days (5.7-28 days; n=60), whereas six patients with no response had a median time to maximum expansion of 20 days (13-63 days). Kymriah uses the 4-1BB costimulatory domain in its chimeric antigen receptor, which has shown to enhance early cellular expansion and long-term endurance of CAR-T cells.

See- "Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia"- Shannon L. Maude, M.D., Ph.D., Theodore W. Laetsch, M.D., Jochen Buechner, M.D., Ph.D., Susana Rives, M.D., Ph.D., , et al.February 1, 2018 N Engl J Med 2018; 378:439-448 DOI: 10.1056/NEJMoa1709866.