Evolution of tisagenlecleucel use for the treatment of pediatric and young adult relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL): Center for International Blood & Marrow Transplant Research (CIBMTR) registry results.
Notice bibliographique
Résumé
10016 Background: Tisagenlecleucel is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell immunotherapy indicated for patients (pts) up to 25 y of age with B-ALL that is refractory or in second or later relapse. Since the pivotal ELIANA trial, pt characteristics now include pts < 3 y, pts with isolated central nervous system relapse, and pts with leukemia burden < 5%. Here we examine the impact of tisagenlecleucel on the pt treatment journey since FDA approval in 2017. Methods: Data were collected as a part of a noninterventional, prospective, longitudinal study using the CIBMTR registry. Pts were treated in the United States, Canada, Korea, or Taiwan. Results: As of May 4, 2023, 974 pts received tisagenlecleucel. Primary disease history has evolved since 2017. Notably, disease burden prior to infusion has decreased (≥50% blasts: 18% in 2018, 4% in 2022) and a higher proportion of pts received tisagenlecleucel while in morphological complete remission (34% in 2018, 51% in 2022). Between 2018 and 2022, the proportion of pts who were in third or greater relapse decreased (14% vs 2%, respectively). Pts ≥18 y had more prior exposure to blinatumomab and inotuzumab compared with pts < 18 y: 27% vs 16% and 17% vs 7%, respectively. The proportion of pts undergoing ≥1 hematopoietic stem cell transplantation (HSCT) before tisagenlecleucel infusion decreased (37% in 2018, 15% in 2022), coinciding with the use of tisagenlecleucel in earlier lines of therapy. Reporting of B-cell recovery was suboptimal. In total, 34.5% (314/911) of pts received postinfusion HSCT (reasons for HSCT were not captured for most pts); 8.5% (77/911) of pts received postinfusion HSCT to treat relapse, persistent/progressive disease, or positive minimal residual disease. Although the overall rate of postinfusion HSCT did not change, pts with high-risk cytogenetics showed a decrease in HSCT frequency. Previously, most pts < 3 y with KMT2A rearrangement received a HSCT. Since 2017, only 16% (12/75) of pts < 3 y received a prior HSCT despite 72% (54/75) having a KMT2A rearrangement. Furthermore, of the pts with rearrangement, only 43% (23/53) received a HSCT postinfusion. With censoring for HSCT, median RFS improved: 18 mo in 2018, 27 mo in 2020, and not estimable in 2021. OS was not substantially affected by HSCT censoring; 36-mo probabilities (95% CI) with and without censoring were 66 (61-71) and 62 (57-66), respectively. Conclusions: Pediatric and young adult pts with r/r B-ALL are receiving tisagenlecleucel earlier in the course of their disease treatment, reducing the use of HSCT for r/r disease, and prolonging RFS. As both real-world and clinical trial data supporting the curative potential of tisagenlecleucel grow, the use of HSCT in pts with remission after CAR-T should be carefully evaluated.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».