Five-year follow-up of tisagenlecleucel in pediatric and young adult patients with R/R B-ALL: ELIANA trial

Introduction

Relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL) remains a challenge to treat in pediatric and young adult populations, historically characterized by poor prognosis and increasing morbidity. Tisagenlecleucel, an autologous CD-19 directed chimeric antigen receptor (CAR) T-cell therapy, showed significant efficacy and a tolerable safety profile in heavily pretreated adults with R/R B-ALL in a primary analysis of the ELIANA phase II trial (NCT02435849).¹ Recently, 3-year results of the ELIANA trial were published in the Journal of Clinical Oncology by Laetsch, et al.² During the European Hematology Association (EHA) 2022 Congress, Susana Rives presented the final results from a 5-year follow-up of patients treated in phase II of the ELIANA trial.³ Below, we summarize the key findings.

Study design

ELIANA is an ongoing, phase II, open-label, multicenter global study in patients aged 3–21 years with R/R B-ALL and bone marrow blasts ≥5%. Patients with prior CD19-directed or gene therapy and isolated extramedullary disease relapse were excluded. Patients ≤50 kg received infusion of tisagenlecleucel at 0.2–5.0 × 10⁶ CAR+ viable T cells/kg and 0.1–2.5 × 10⁸ CAR+ viable T cells for patients >50 kg. Lymphodepletion therapy prior to infusion included fludarabine 30 mg/m² (IV daily for four doses) and cyclophosphamide 500 mg/m² (IV daily for two doses). 

The primary endpoint was overall remission rate, defined as the complete remission (CR) rate + complete remission with incomplete hematologic recovery (CRi). Secondary endpoints included minimal residual disease status, relapse-free survival (RFS), duration of response, overall survival (OS), event-free survival (EFS), cellular kinetics, and safety.

Baseline characteristics

A total of 79 patients were infused with tisagenlecleucel with a median age of 11 years, 57% were male. All patients were heavily pretreated with a median of three prior lines of therapy and 61% had prior allogeneic hematopoietic stem cell transplantation (AlloSCT). All patients had a high leukemic burden at induction (Table 1).

Table 1. Baseline and clinical characteristics*

Efficacy

• The overall remission rate was 82% at Month 3 (Figure 1) and 98% of these patients had minimal residual disease negative status.
• Among the 65 patients who attained the primary endpoint (CR/CRi within 3 months), the RFS rate was 44% after 5 years, with a median RFS of 43 months.
• Median time to B-cell recovery was 39 months in responders and the probability of B-cell aplasia at 6 and 12 months was 83% and 71%, respectively.
• Among patients in remission, 25% of patients subsequently underwent AlloSCT.
• EFS comparison at 5 years of those without censoring for AlloSCT and those with censoring were 36% and 34%, respectively, with a median EFS of 15 months.
• Median OS was not reached and 5-year OS was 55%.
• There were no significant differences in EFS and OS endpoints between pediatric and young adult patients.

Figure 1. Response rates at Month 3 in patients with R/R B-ALL infused with tisagenlecleucel*

ALL, acute lymphoblastic leukemia; CR, complete remission; Cri, CR with incomplete hematologic recovery; ORR, overall remission rate; R/R, relapsed/refractory.
*Adapted from Rives.²

Safety

Overall, 39% of patients experienced at least one adverse event (AE) of special interest of any grade >1 year post infusion. The most common AEs of any grade and Grade ≥3 were infection in 23 (33%) and 14 (20%) patients, respectively, and hematologic disorders including cytopenias in seven (10%) and four (6%) patients, respectively. Two deaths were reported in remission and no new treatment-related AEs were observed in the 5-year follow up.

Conclusion

This study demonstrated the long-term durable efficacy and safety of tisagenlecleucel in heavily pretreated pediatric and young adult patients with R/R B-ALL. With no new safety events reported and continued efficacy seen at 5 years, tisagenlecleucel therapy continues to show promise as a treatment option for pediatric and adult patients with R/R B-ALL.