Updated Analysis of ELIANA Trial Shows Longer-Term Durable Remissions With Tisagenlecleucel in Children, Young Adults With Relapsed/Refractory ALL

Key Points

  • In the analysis of 75 infused patients with 3 or more months of follow-up, tisagenlecleucel demonstrated an overall remission rate of 81%.
  • Remissions were durable with 6-month relapse-free survival of 80%. Event-free survival was 73% at 6 months and 50% at 12 months, with median event-free survival not reached.
  • Overall survival in the 75 infused patients was 90% at 6 months, and 76% at 12 months.

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.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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