Leukapheresis and Tisagenlecleucel Manufacturing Outcomes in Patients Age <3 Years with Relapsed/Refractory Acute Lymphoblastic Leukemia
Bibliographic record
Abstract
Tisagenlecleucel is approved for the treatment of relapsed/refractory (r/r) B cell acute lymphoblastic leukemia (B-ALL) in patients up to age 25 years based on the results of a pivotal trial (ELIANA) in pediatric and young adult patients. However, that trial did not include patients age <3 years because of the challenges posed by leukapheresis of very young and low-weight patients. Data on leukapheresis material and manufacturing outcomes among patients age <3 years have been collected since the time of global regulatory approval. Here we report leukapheresis characteristics and manufacturing outcomes for tisagenlecleucel produced for patients age <3 years in US and non-US commercial settings. Qualified patients with r/r B-ALL were age <3 years at the time of request for commercial tisagenlecleucel, with manufacturing data starting after August 30, 2017 (date of first US Food and Drug Administration approval). Leukapheresis and manufacturing outcomes data were stratified by age and weight. CD3+ cell count and CD3+/total nucleated cell (TNC) percentages were obtained from the leukapheresis material; leukocyte subpopulations were obtained via quality control vials. Of the 146 tisagenlecleucel quality control batches analyzed for CD3+ cell count and CD3+/TNC%, 86 batches (84 patients) were from US sites and 60 batches were from non-US sites. The median patient age and weight were 1.2 years and 10.4 kg at US sites and 1.5 years and 10.5 kg at non-US sites. Globally, 137 of 146 batches (94%) were manufactured within specifications across 16 countries. Among tisagenlecleucel batches manufactured in the United States between 2017 and 2021, there was a trend toward increasing CD3+ counts, CD3+/TNC%, and manufactured dose of chimeric antigen receptor (CAR) T cells; there was no difference in median days of collection by patient age or weight. Globally, a trend toward 1 or more potential additional collection days was observed for patients weighing ≤10 kg. Leukapheresis and tisagenlecleucel manufacturing in pediatric patients with r/r B-ALL age <3 years, including infants (<1 year), and low weight are feasible. As global experience with leukapheresis and patient identification for CAR-T cell therapy increased over time, a corresponding improvement in tisagenlecleucel manufacturing success has been observed. Clinical outcome data for these patients are currently being explored.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".