Clinical Summary: 

• Design/Population: In the phase 2 COG AALL1721/CASSIOPEIA trial, children and young adults with high-risk B-cell acute lymphoblastic leukemia and persistent MRD after consolidation received tisagenlecleucel.
• Key Outcomes: Tisagenlecleucel produced durable remissions, high MRD-negative rates, and encouraging long-term survival with low rates of severe cytokine release syndrome and neurotoxicity.
• Clinical Relevance: These findings suggest that tisagenlecleucel may improve outcomes in a very high-risk population historically associated with poor disease-free survival.

Results from the phase 2 COG AALL1721/CASSIOPEIA trial demonstrated that tisagenlecleucel produced durable remissions in adolescent and young adult patients with high-risk B-cell acute lymphoblastic leukemia (B-ALL) and persistent minimal residual disease (MRD) during frontline therapy.

These results were presented by Shannon Maude, MD, PhD, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In this study, 121 patients between 1 and 25 years of age with persistent MRD of at least 0.01% by flow cytometry at the end of consolidation received a single infusion of tisagenlecleucel (0.2-5×10⁶ CAR+ T cells/kg for patients ≤50 kg or 0.1-2.5×10⁸ CAR+ T cells for patients >50 kg) following standard lymphodepleting chemotherapy. Reinfusion was permitted for patients with B-cell recovery within 6 months and/or MRD of at least 0.01% at any time. Primary end points included 4-year overall survival (OS) and 5-year disease-free survival (DFS). Key secondary end points included MRD negativity and safety.

At a median follow-up of 38 months, the 4-year OS rate was 85%. DFS without censoring for new therapy was 71% at 3 years and 64% at 5 years. MRD negativity was achieved in 95% of patients at day 29 and 86% at 3 months after infusion. Relapse occurred in 31 patients, including 7 relapses after new therapy or stem cell transplant. Overall, 41 patients received a second tisagenlecleucel infusion, and 58 patients received new anticancer therapy or stem cell transplant without prior relapse. Median duration of B-cell aplasia was 5.6 months. The probability of ongoing remission with B-cell aplasia was 76% at 3 months, 47% at 6 months, and 31% at 12 months.

Following first infusion, cytokine release syndrome was reported in 37% of patients, including grade ≥3 events in 2% of patients. Immune effector cell-associated neurotoxicity syndrome was reported in 3% of patients, including grade ≥ 3 events in 1% of patients. There were 18 deaths, all occurring after new therapy, stem cell transplant, and/or relapse.

“Durable remissions, with very low rates of severe CRS/ICANS, were achieved with [tisagenlecleucel] in a [very high-risk] population with persistent MRD in frontline therapy, who historically have low 5 [year] DFS… [however] longer follow-up is needed to confirm 5 [year] DFS,” concluded Dr Maude. 

Source: 

Maude S, Rives S, Krueger J, et al. Tisagenlecleucel (tisa-cel) in pediatric and young adult patients with high-risk (HR) B-cell acute lymphoblastic leukemia (B-ALL) and minimal residual disease (MRD) at the end of frontline consolidation (EOC). Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 10000.