Tisagenlecleucel Shows Durable Five-Year Remissions in Pediatric and Young Adult Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia

Five-Year Follow-Up Results from the Phase 2 ELIANA Trial 

Clinical Summary:

• Design/Population: The global phase 2 ELIANA trial evaluated a single infusion of tisagenlecleucel in pediatric and young adult patients aged 3 to 25 with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). 
• Key Outcomes: Tisagenlecleucel produced durable long-term disease control, with approximately half of responders remaining relapse free at 5 years and median overall survival not reached. No new or unexpected safety signals or secondary T-cell malignancies emerged with extended follow-up. 
• Clinical Relevance: Durable remissions were observed despite relatively limited use of post–CAR T-cell transplantation, supporting tisagenlecleucel as a potential definitive therapy for selected pediatric and young adult patients with heavily pretreated relapsed or refractory B-ALL rather than solely as a bridge to transplantation.

Five-year follow-up results from the pivotal phase 2 ELIANA trial demonstrated durable remissions and long-term survival with tisagenlecleucel in pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), with no new or unexpected safety signals identified.

“Allogeneic stem cell transplantation had been considered the best chance for a cure in patients with B-ALL… however, not all patients are eligible,” stated Stephan Grupp, MD, PhD, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, and coauthors. “CAR-T cell therapy can induce deep remission, increasing transplant eligibility, but the curative potential of CAR-T cell therapy alone—especially in patients who do not proceed to [stem cell transplantation]—has yet to be established.” 

This global trial enrolled 79 patients aged 3 to 25 years with relapsed or refractory B-ALL who received a single infusion of tisagenlecleucel, with weight-based dosing for patients weighing ≤50 kg. The median follow-up was 79.4 months, extending substantially beyond the previously reported 3-year analysis. Notably, 61% of patients had undergone stem cell transplantation before receiving infusion. 

At analysis, 88.6% of patients achieved a best overall response of complete remission or complete remission with incomplete blood count recovery. Among the 65 patients who achieved complete remission or complete remission with incomplete blood count recovery within 3 months of infusion, 33 patients subsequently relapsed, including 8 patients with CD19-positive and 18 patients with CD19-negative disease.

Among all responders, estimated 5-year relapse-free survival (RFS) was 47.3% when censoring included subsequent stem cell transplantation and 51% when stem cell transplantation was excluded from censoring. Among patients who achieved complete remission or complete remission with incomplete blood count recovery within 3 months, corresponding 5-year RFS rates were 49.3% and 53.2%, respectively. Median RFS was 46.8 months when subsequent stem cell transplantation was included in censoring and was not estimable when stem cell transplantation was excluded.

Long-term overall survival (OS) was also observed. Among all infused patients, median OS was not reached. Estimated 5-year OS was 55% when censoring included subsequent stem cell transplantation and 62.4% when stem cell transplantation was excluded. 

Eighteen patients underwent stem cell transplantation after tisagenlecleucel infusion, including 17 responders, 14 of whom were still in complete remission at the time of transplantation. The similar 5-year RFS estimates when subsequent stem cell transplantation was included or excluded from censoring suggest that durable disease control with tisagenlecleucel may not depend on consolidative transplantation for all patients.

Evidence of sustained CAR T-cell activity was also observed. B-cell aplasia persisted in 40 of 65 patients who achieved complete remission or complete remission with incomplete blood count recovery within 3 months, and median time to B-cell recovery was not reached when censoring for subsequent anticancer therapies, including stem cell transplantation.

No new or unexpected safety signals emerged with extended follow-up. Among 49 patients monitored for more than 1 year after infusion, 24 patients experienced at least 1 long-term adverse event. Since the previous 3-year analysis, 4 additional deaths occurred, all attributed to disease relapse. One secondary malignancy was reported, with no secondary T-cell malignancies observed.

“Altogether, the durable efficacy, absence of new safety signals, and prior patient-reported quality of life improvements support the potential of tisagenlecleucel as definitive therapy for many heavily pretreated pediatric and young adult patients with [relapsed or refractory] ALL,” concluded Dr Grupp et al. 

Source:

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