Tisa-Cel Yields Enduring Remissions in Younger High-Risk B-ALL Population

Tisagenlecleucel (tisa-cel; Kymriah) produced durable remissions among pediatric and young adult patients with high-risk B-cell acute lymphoblastic leukemia (B-ALL) and minimal residual disease (MRD) following frontline consolidation therapy, according to a presentation on findings from the phase 2 CASSIOPEIA/COG AALL1721 trial (NCT03876769) at the European Hematology Association (EHA) 2026 Congress.¹

The estimated overall survival (OS) rate at 4 years was 85% (95% CI, 76%-90%), which fulfilled the trial’s primary end point of an OS rate exceeding 80% with a lower CI bound of more than 65%. The disease-free survival (DFS) rate when censoring for new anticancer therapy—including stem cell transplantation (SCT)—was 71% (95% CI, 61%-79%) at 3 years and 64% (95% CI, 53%-73%); the median DFS was not evaluable (NE; 63-NE). In an analysis censoring for the aforementioned factors, the DFS rates were 69% (95% CI, 55%-79%) at 3 years and 62% (95% CI, 46%-74%), with a median value of 63 months (95% CI, 45-NE). The study investigators noted a need for longer follow-up to formally evaluate 5-year DFS.

Data showed that relapses occurred in 31 patients, which included 7 after receipt of new therapy or SCT. Additionally, 48% (n = 58) of patients received new anticancer therapy without prior relapse, which included SCT in 30 patients.

The median duration of B-cell aplasia was 5.6 months (n = 118). The likelihood of ongoing B-cell aplasia was 76% (95% CI, 67%-83%) at 3 months, 47% (95% CI, 38%-56%) at 6 months, and 31% (95% CI, 23%-41%) at 12 months. Additional data showed that 41 patients received a reinfusion with tisa-cel, which included 37 (90%) with early B-cell recovery before 6 months and 4 (10%) with MRD positivity. At the time of the analysis, 6 patients with early B-cell recovery had sustained an ongoing complete remission (CR) without any new anticancer therapy, although 3 underwent reinfusion with tisa-cel.

“In summary, durable remissions were achieved with tisa-cel in patients with very high-risk B-ALL who were MRD positive at the end of consolidation, and this was achieved with very low rates of cytokine release syndrome [CRS] and immune effector cell-associated neurotoxicity syndrome [ICANS],” Shannon L. Maude, MD, PhD, an attending physician in the Cancer Center at The Children’s Hospital of Philadelphia, stated in the presentation.¹ “Future work needs to focus on what the risk of relapse and shorter persistence [is] in this population and frontline therapy to determine if other therapy is needed.”

The phase 2 CASSIOPEIA trial was designed to assess the anti-CD19 CAR T-cell therapy tisa-cel among pediatric and young adult patients with very high-risk B-ALL and MRD positivity at the end of consolidation therapy.² A total of 121 patients received tisa-cel at 0.2 to 5.0 x 10⁶ CAR-positive viable T cells per kg with a body weight of no more than 50 kg or 0.1 to 2.5 x 10⁸ cells/kg with a body weight of more than 50 kg.

The trial’s primary end points included OS at 4 years and DFS at 5 years without censoring for new anticancer therapy. Secondary end points included DFS with censoring and safety.

Patients 1 to 25 years old with de novo high-risk B-ALL per NCI criteria as well as first CR after frontline induction and consolidation therapy plus MRD expression of at least 0.01% per flow cytometry at end of consolidation were eligible for enrollment on the trial. Those with Philadelphia chromosome–positive disease or hypodiploid ALL were ineligible for study entry.

The median patient age was 14.0 years (range, 1-24), and most were 10 to 17 years old (64%) and male (67%). Most patients had MRD expression of at least 0.01% but no more than 0.1% (53%). Of note, 8 patients (7%) had KMT2A or MLL rearrangements, and 7 (6%) had Down syndrome. Across the study population, 97 were still receiving treatment at the time of analysis.

Cellular kinetic data showed that the persistence of CAR T cells was reported for a maximum of 5 years and was typically shorter in patients with B-cell recovery.

Adverse effects (AEs) of any grade and grades 3 or higher occurred in 97% and 67% of patients, respectively. The most common toxicities of any grade included decreased neutrophil counts (40%), CRS (37%), and headaches (33%), while the most frequent grade 3 or higher AEs included decreased neutrophil counts (39%), decreased white blood cell counts (23%), and decreased lymphocyte counts (21%).

Safety data showed that 3 patients had ICANS; 1% of the population experienced grade 3 or higher events. Additionally, there were no secondary malignancies. There were 18 deaths, which all occurred after new therapy and/or relapse at more than 30 deaths following tisa-cel infusion.

The most common grade 3 or higher cytopenias at week 4 and beyond included lymphopenia (40%), neutropenia (26%), leukopenia (23%), thrombocytopenia (14%), and anemia (1%). Of note, most patients with grade 3 or higher cytopenias at week 4 had their toxicities resolve by month 6.

Disclosures: Maude noted serving on a study steering committee and receiving clinical trial support in relation to Novartis, Wugen, and Autolus. She also noted serving on an advisory board with Syndax.

References

1. Maude SL, Rives S, Krueger J, et al. Tisagenlecleucel in pediatric and young adult patients with high-risk B-cell acute lymphoblastic leukemia and minimal residual disease at the end of frontline consolidation. Presented at the European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S135.
2. Study of efficacy and safety of tisagenlecleucel in HR B-ALL EOC MRD positive patients (CASSIOPEIA). ClincialTrials.gov. Updated June 2, 2026. Accessed June 11, 2026. https://tinyurl.com/bddjy2ta