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 US Food and Drug Administration (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%). 60% 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. Any grade treatment-related adverse events (AE) occurred in 95% of patients, with the most common non-hematologic AEs being cytokine release syndrome (CRS; 77%), pyrexia (40%), decreased appetite (39%), febrile neutropenia (36%) and headache (36%). 73% of patients experienced a grade 3/4 treatment-related AE. CRS, a known complication of Kymriah that may occur when engineered cells become activated in the patient's body, occurred in 77% of patients. 46% of patients experienced grade 3/4 CRS (grade 3: 21%; grade 4: 25%), using the Penn Grading Scale, a rigorous scale for grading CRS. CRS was managed globally using prior site education on implementation of the CRS treatment algorithm. Thirty-five of 75 infused patients (47%) were admitted to the intensive care unit for management of CRS. Neurological events occurred in 40% of patients within eight weeks of infusion, and 13% (n=10) of patients had grade 3, which were managed with best supportive care. No incidence of grade 4 neurological events or cerebral edema was reported. Eighteen patients (24%) received Kymriah in the outpatient setting. To support safe patient access, Kymriah is only available through a network for certified treatment centers throughout the country which are fully trained on the use of Kymriah and appropriate patient care.