Tisagenlecleucel Yields Promising Disease-Free Survival in High-Risk Pediatric ALL: Shannon L. Maude, MD, PhD

Earlier today, The American Journal of Managed Care^® spoke with lead investigator Shannon L. Maude, MD, PhD, about her abstract, “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,” ahead of the presentation of the findings at the European Hematology Association 2026 Congress in Stockholm, Sweden.

Maude explained that the phase 2 CASSIOPEIA/COG AALL1721 trial (NCT03876769) enrolled pediatric patients with high-risk acute lymphoblastic leukemia (ALL) who had persistent minimal residual disease (MRD) after 2 cycles of chemotherapy, a population with historically poor outcomes and a 5-year disease-free survival (DFS) rate of roughly 39%. Because outcomes in this group have been so poor, bone marrow transplant has traditionally been the standard of care. Consequently, the trial’s primary goal was to improve 5-year DFS, with overall survival as a secondary end point.

The regimen consisted of approximately 5 months of chemotherapy followed by chimeric antigen receptor (CAR) T-cell infusion, specifically tisagenlecleucel (Kymriah; Novartis). Results showed a meaningful improvement in 5-year DFS, although Maude noted that longer follow-up is needed to confirm the findings. In addition, a substantial proportion of patients achieved MRD negativity, which she highlighted as a critical benchmark given that all enrolled patients were MRD-positive at baseline; Maude emphasized that converting patients to MRD-negative status is itself an important achievement in this high-risk population.

Not all patients were managed with CAR T-cell therapy alone. Some went on to receive additional treatment, including a bone marrow transplant. However, Maude explained that the trial successfully reduced the number requiring transplant from what otherwise would have been essentially universal. The primary driver of escalation to additional therapy was early loss of CAR T-cell persistence, which, based on data from relapsed and refractory settings, is associated with higher relapse risk; B-cell aplasia was used as a surrogate marker for ongoing CAR T-cell persistence.

One of the key unanswered questions, Maude said, is whether durable CAR T-cell persistence is truly necessary in this frontline, low-disease-burden population, or whether even patients with early CAR T loss can still achieve deep, lasting remissions. She noted that the question will require longer follow-up to answer.

Regarding the safety profile, cytokine release syndrome and other toxicities were less severe than expected due to patients’ low disease burden at enrollment. Maude said that whether CAR T-cell persistence is necessary for durable remission in this frontline setting remains a key area for future research.

“It’s very encouraging in this population, who, with intensive chemotherapy or with bone marrow transplant, would likely have significant toxicities, so I think we need to look at long-term follow-up in more detail, and we need to really look at whether persistence is key in this population or if these patients, even with short persistence, can have a deep remission that will be durable,” she concluded.