Building Capacity for Relapsed/Refractory ALL Patients Needing CAR-T Cells: How Do We Prepare?
Notice bibliographique
Résumé
Abstract Introduction: The prognosis of relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL) remains poor in adults. Response rates and survival following anti-CD19 chimeric antigen receptor (CAR) T-cells in r/r ALL have exceeded those of other available agents, but comparative studies are still lacking. Although this therapy shows great promise, it involves complex and expensive manufacturing and administration. Our study seeks to understand the response and survival outcomes of a cohort of Canadian patients with ALL treated with current standard therapies to help the Canadian health care system build capacity for anti-CD19 CART therapies for r/r ALL. Methods: We conducted a retrospective chart review of all patients diagnosed with ALL at 2 large Canadian academic hospitals between 2010 and 2015 (Ottawa and Vancouver). All patient, therapy and outcome-based factors were extracted. Included patients were then cross-checked against the eligibility criteria for completed anti-CD19 CART cell trials in r/r ALL, but with an upper age cut-off of 75. Results: 173 patients were diagnosed with ALL over a 5-year period, with median age of 50 (range 16-88). 159 (92%) patients had CD19 reported by flow cytometry, of which 141 were positive at diagnosis. 124 patients (72%) achieved complete remission with induction chemotherapy and 74 patients (43%) relapsed after a median of 11.8 months (range 1-85.6) from diagnosis, of which 29 patients (17%) experienced a second relapse. A total of 63 patients (36%) had an allogeneic stem cell transplant, of which 22 (13%) relapsed after transplant. Patients who relapsed at any point in time survived 5.4 months (range 0.2-55.4). A total number of 62 patients (35.8%) would have been eligible for currently approved anti-CD19 CAR T cell therapy. Reasons for ineligibility were not limited to remission status, but also included CNS involvement, previous solid malignancy, undocumented CD19 status or CD19 negativity, and evidence of kidney or liver dysfunction. The median event-free and overall survival for patients who would have been eligible for FDA-approved anti-CD19 CART cells were 10.3 months (range 0.4-52.3) and 17.3 months (range 0.4-72.6), respectively. Conclusion: Anti-CD19 CAR T cell therapy has shown very promising results based on early phase data in patients with r/r ALL. Canadian patients are expecting this therapeutic option to be available soon, but our health care system needs to prepare for the complexity of this therapy. Our study helps provide "real-world" eligibility and outcomes of adult patients with r/r ALL. This data suggests that about one-third of cases of ALL could be eligible for this new therapy and should help centers build capacity according to how many new cases of ALL are seen per year. Disclosures No relevant conflicts of interest to declare.
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 | 0,011 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,003 | 0,002 |
| Communication savante | 0,004 | 0,002 |
| Science ouverte | 0,002 | 0,002 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,007 | 0,001 |
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 ».