Updated Analysis of ELIANA Trial Shows Longer-Term Durable Remissions With Tisagenlecleucel in Children, Young Adults With Relapsed/Refractory ALL
Updated results from the ELIANA clinical trial of tisagenlecleucel (Kymriah), formerly CTL019, in relapsed or refractory pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL) have been published by Maude et al in The New England Journal of Medicine. New data include longer-term follow-up and efficacy in 75 infused patients, analysis of expansion and persistence of tisagenlecleucel, and longer-term safety.
New Analysis Findings
In the analysis of 75 infused patients with 3 or more months of follow-up, tisagenlecleucel demonstrated an overall remission rate of 81% (95% confidence interval [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 6-month relapse-free survival of 80%. Event-free survival was 73% at 6 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 6 months, and 76% (95% CI = 63%–86%) at 12 months. Tisagenlecleucel was detected in patients up to 20 months. Median persistence of tisagenlecleucel was 168 days (range, 20–617; n = 60 patients with CR/CRi) at data cutoff. All responding patients demonstrated B-cell aplasia, an on-target effect of treatment with tisagenlecleucel, 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). Tisagenlecleucel 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.
Adverse Events and Safety
Any grade treatment-related adverse events occurred in 95% of patients, with the most common nonhematologic adverse events being cytokine release syndrome (CRS; 77%), pyrexia (40%), decreased appetite (39%), febrile neutropenia (36%) and headache (36%). Seventy-three percent of patients experienced a grade 3/4 treatment-related adverse event. CRS, a known complication of tisagenlecleucel that may occur when engineered cells become activated in the patient's body, occurred in 77% of patients. Forty-six percent 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. Neurologic events occurred in 40% of patients within 8 weeks of infusion, and 13% (n = 10) of patients had grade 3 events, which were managed with best supportive care. No incidence of grade 4 neurologic events or cerebral edema was reported. Eighteen patients (24%) received tisagenlecleucel in the outpatient setting. To support safe patient access, tisagenlecleucel is only available through a network for certified treatment centers throughout the country which are fully trained on the use of tisagenlecleucel and appropriate patient care.
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