Pretreatment Disease Burden and Outcomes With Commercial Tisagenlecleucel in Pediatric/Young Adult B-Cell ALL

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In an analysis from the Pediatric Real-World Chimeric Antigen Receptor Consortium reported in the Journal of Clinical Oncology, Schultz et al found that pretreatment high disease burden was associated with poorer outcomes in pediatric and young adult patients who received commercial tisagenlecleucel for relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

As stated by the investigators, “Tisagenlecleucel is … approved for children, adolescents, and young adults with relapsed and/or refractory B-cell ALL…. [R]egistration for tisagenlecleucel was based on a complete response rate of 81%, 12-month overall survival of 76%, and event-free survival of 50%.”

Study Details

The retrospective study included pediatric, adolescent, and young adult patients from 15 U.S. sites who had leukapheresis shipment to the manufacturer for commercial tisagenlecleucel between August 2017 and March 2020. A total of 197 evaluable patients were included in an intent-to-treat response analysis, with 184 evaluable patients who underwent infusion included in survival analysis. Pretreatment high disease burden was defined as ≥ 5% bone marrow lymphoblasts, any peripheral blood lymphoblasts, CNS3 disease, or non­–central nervous system extramedullary disease.

Key Findings

The median age at tisagenlecleucel infusion was 12 years. The median follow-up from infusion was 335 days (range = 6–863). Among 184 patients receiving infusion, 94 (51%) had high disease burden, 41 (22%) had low disease burden, 46 (25%) had undetectable disease, and 4 had indeterminate disease burden.

The intent-to-treat response analysis showed morphologic complete response at day 28 in 156 (79%, 95% confidence interval [CI] = 72%–84%) of 197 patients. Among the 184 infused patients, a morphologic complete response was observed in 156 (85%, 95% CI = 79%–89%). In the infused cohort, response rates were 73% among patients with high disease burden vs 98% in those with low disease burden and 100% in those with undetectable disease (overall P < .0001).

In the total infused cohort, 12-month overall survival and event-free survival rates were 72% and 50%, respectively. Respective rates were 58% and 31% among patients with high disease burden, compared with 85% and 70% among those with low disease burden and 95% and 72% among those with undetectable disease (overall P < .0001). On multivariate analysis for overall survival, the hazard ratio for the high disease burden group vs the undetectable disease group was 5.10 (95% CI = 1.79–14.6, P = .002).

Among all infused patients, grade ≥ 3 cytokine-release syndrome and neurotoxicity rates were 21% and 7%, with rates of 35% and 9% in patients with high disease burden.

The investigators concluded, “Commercial tisagenlecleucel in pediatric, adolescent, and young adult patients with relapsed or refractory [B-cell] ALL demonstrates efficacy and tolerability. This first analysis of commercial tisagenlecleucel stratified by disease burden identifies high disease burden preinfusion to associate with inferior overall survival and event-free survival and increased toxicity.”

Liora M. Schultz, MD, of the Division of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by a St. Baldrick’s/Stand Up 2 Cancer Pediatric Dream Team Translational Cancer Research grant and the Virginia and D.K. Ludwig Fund for Cancer Research. For full disclosures of the study authors, visit

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