Tisagenlecleucel Shows Durable Efficacy in Pediatric/Young Adult ALL

Tisagenlecleucel (tisa-cel; Kymriah) continued to demonstrate durable responses and a manageable long-term safety profile in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), according to a 5-year analysis of the phase 2 ELIANA trial (NCT02435849) published in the Journal of Clinical Oncology.

How effective was tisa-cel in the ELIANA trial?

At a median follow-up of 79.4 months (range, 59.7-90.3), the estimated 5-year relapse-free survival (RFS) rate among all responders (n = 70) was 47.3% (95% CI, 33.3%-60.1%) with censoring for all further anticancer therapies, including stem cell transplantation (SCT). The 5-year RFS was 51.0% (95% CI, 37.6%-62.8%) with censoring for further anticancer therapies except SCT. Among patients with a sustained best overall response of complete response (CR) or CR with incomplete blood count recovery (CRi) within 3 months (n = 65), the median RFS was 46.8 months (95% CI, 17.8-not estimable [NE]). Overall, 70 of 79 patients (88.6%) achieved a best overall response of CR/CRi. The median overall survival (OS) for all infused patients was not reached, with an estimated 5-year OS of 55.0% (95% CI, 41.4%-66.7%) and 62.4% (95% CI, 50.2%-72.4%) with and without inclusion of SCT in censoring, respectively.

Among patients weighing 50 kg or less who received weight-based dosing, the 5-year RFS rate was 71.1% (95% CI, 46.4%-85.9%) in those above the median dose vs 41.9% (95% CI, 19.1%-63.3%) at or below it. Among patients heavier than 50 kg who received flat dosing, the 5-year RFS rate was 72.9% (95% CI, 27.6%-92.5%) vs 11.4% (95% CI, 0.6%-39.4%), respectively. The median dose was 3.0 x 10⁶ cells/kg. Disease relapse occurred in 33 of 65 patients who maintained remission within 3 months; 8 (24%) were CD19-positive relapses, and 18 (55%) were CD19-negative relapses. The median time to B-cell recovery was not reached.

How safe was tisa-cel in the ELIANA trial?

No new or unexpected adverse events (AEs) were reported. Among 49 patients monitored for more than 1 year following infusion, 4 new deaths had occurred since the 3-year update, all attributed to relapse. Furthermore, 58 additional AEs were reported, including 21 grade 3 or higher AEs, which were most frequently infections (n = 9) and respiratory events (n = 4).

One patient experienced a secondary malignancy, and no secondary T-cell malignancies were reported. B-cell aplasia was sustained in 40 of 65 patients (62%) who achieved CR/CRi within 3 months.

“The long-term analysis of the pivotal phase 2 ELIANA trial continues to demonstrate durable responses to tisagenlecleucel with a manageable long-term safety profile,” lead author Stephan A. Grupp, MD, PhD, section chief of the Cellular Therapy and Transplant Section at Children's Hospital of Philadelphia, wrote in the publication with study coinvestigators. “These findings continue to support the potential of tisagenlecleucel as definitive therapy for many heavily pretreated pediatric and young adult patients with [relapsed/refractory] B-ALL.”

How was ELIANA designed?

ELIANA was a global, multicenter, phase 2 study of tisagenlecleucel in patients aged 3 to 25 years with relapsed/refractory B-ALL, administered as a single infusion with dosing normalized by weight in patients weighing 50 kg or less. The first patient’s first visit occurred on April 8, 2015, and as of the last patient’s last visit on November 17, 2022, 79 patients had received an infusion; 61% had received SCT before tisagenlecleucel infusion. Patients followed for 5 years were eligible to enroll in the companion PAVO study (NCT02445222) for 15 years of follow-up, and 26 patients transitioned into PAVO.²

Key long-term end points in this analysis included RFS, OS, and safety. The pivotal trial's primary end point was overall remission rate within 3 months of infusion.

The authors noted that, despite improved outcomes in ELIANA and in post-approval real-world studies, discussion continues regarding the use of CAR T-cell therapy combined with SCT. In this analysis, 18 patients received a post-infusion SCT, including 17 responders, 14 of whom were still in CR at the time of transplantation.

References

1. Grupp SA, Maude SL, Rives S, et al. Long-term clinical outcomes of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory ALL. J Clin Oncol. Published online July 29, 2026. doi:10.1200/JCO-25-01471
2. CAR-T long term follow up (LTFU) study (PAVO). ClinicalTrials.gov. Updated October 28, 2025. Accessed August 5, 2026. https://tinyurl.com/yc4y8tv5