Long-term remission rates after treatment with tisagenlecleucel in paediatric and young adult patients with R/R B-ALL

November 2022 Clinical practice Jolien Blokken

Paediatric and young adult patients with R/R B-ALL have very poor prognosis. In the primary analysis of the global phase II ELIANA trial, tisagenlecleucel provided high remission rates in these patients, with more than half of responders remaining relapse-free at two years. After more than five years of follow-up, tisagenlecleucel continues to demonstrate durable efficacy without late adverse effects. In this manner, tisagenlecleucel continues to be a potentially curative treatment option for paediatric and young adult patients with R/R B-ALL.

Paediatric and young adult patients with R/R B-ALL have very poor prognosis, characterised by diminishing likelihood of a cure and increasing morbidity with each additional line of salvage therapy. Tisagenlecleucel is an autologous CD19-directed chimeric antigen receptor (CAR)T-cell therapy that has been approved for this patient population. In the primary analysis of the global phase II ELIANA trial, tisagenlecleucel provided high rates of remission (> 80%) in children and young adults with R/R B-ALL, with 62% of responders remaining relapse-free at 24 months. During her presentation at EHA 2022, Dr. Rives reported the updated efficacy and safety analyses in these patients, with a follow-up of at least five years, and a maximum of 5.9 years post-tisagenlecleucel infusion.

Study design

Eligible patients had advanced R/R B-ALL with ≥ 2 relapses after allo-transplant, or were refractory to at least two lines. All patients were at morphological relapse at inclusion (≥ 5% lymphoblasts). Exclusion criteria were isolated extramedullary disease relapse and prior CD19-directed or gene therapy. Patients received a single infusion of tisagenlecleucel at 0.2-5.0×106 CAR+ viable T cells/kg body weight for patients ≤50 kg and 0.1-2.5×108 CAR+ viable T cells for patients >50 kg. The primary endpoint was overall response rate (ORR), defined as complete remission within three months. Secondary endpoints were MRD status, survival analysis, cellular kinetics, and safety.


In total, 97 patients were enrolled, and 79 patients (81%) received tisagenlecleucel. Of these patients, the median age was eleven years old (range, 3-24) at study entry, and 45 patients were male.  Patients were heavily pre-treated with a median of three prior lines of therapy (range, 1-8), and more than half had prior stem cell transplant (SCT). All patients had high leukemic burden. The median morphologic blast count in the bone marrow was 74%. Of the 79 infused patients, 65 patients (82%) achieved an overall response, of which 49 (62%) were in complete response. Median relapse-free survival (RFS) was 43 months. At five years, the probability among responders to remain relapse-free was 44%. Median time to B-cell recovery was 39 months in responders. The probability of B-cell aplasia was 83% at six months, and 71% at twelve months. Patients with B-cell recovery experienced a 2-year cumulative incidence of relapse of 40%. Among the patients who achieved remission, ten (14%) were transplanted as consolidation, and seven (10%) were transplanted after having relapsed. Median event-free survival was fifteen months. The probability of being event-free at five years without censoring for alloSCT was 36%, and 34% with censoring for alloSCT. Although OS was not reached, the probability of being alive at five years was 55% (95%CI, 43-66%) in all 79 infused patients. OS and EFS were comparable between paediatric and young adult (18-25 years old) patients (with or without censoring for allo-transplant).

No new or unexpected adverse events of special interest (AESI) were reported during the long-term follow-up. After more than one year after infusion, 39% of the patients presented at least one AESI. One patient had cytokine release syndrome (CRS), but this was related to a COVID-19 infection. Two patients had serious neurological events. One-third of the patients presented infection, 20% of them grade 3 or more. Two patients died in remission.  Seven (10%) of the patients had persistent cytopenias more than a year after infusion, and four (6%) were grade 3 or more. One patient displayed myelodysplasia as secondary malignancy.


With more than five years of follow-up, the ELIANA study showed continued durable efficacy of tisagenlecleucel without late adverse effects in heavily pre-treated paediatric and young adult patients with R/R B-ALL. The long-term remission rates demonstrate that tisagenlecleucel may be a curative option for heavily pre-treated and young adult patients with R/R B-ALL.


Rives S, et al. Tisagenlecleucel in pediatric and young adult patients (pts) with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL): final analyses from the ELIANA study. Presented at EHA 2022; Abstract S112.