Real-world barriers to CAR-T access: A Canadian referral center perspective.
Notice bibliographique
Résumé
e19002 Background: CD19 chimeric antigen receptor T-cell (CAR-T) is the standard of care for patients with relapsed or refractory large B-cell lymphoma (LBCL) beyond second line therapy. Access to CAR-T remains a significant barrier for patients and is limited by the numbers of CAR-T centers, patient comorbidities and lymphoma kinetics. This study aims to define clinical features associated with CAR-T ineligibility and associated outcomes in a real-world setting. Methods: We conducted a single center retrospective study of all adult patients with R/R LBCL referred at Hôpital Maisonneuve-Rosemont in Montreal, Canada, for CAR-T between July 2019 and December 2023. Comprehensive data were gathered from electronic medical records. This study was approved by the institutional ethics committee. Results: A total of 235 patients were evaluated: 133 (57%) were infused, 10 (4%) were apheresed but not infused and 92 (39%) patients were deemed ineligible and further analyzed. The main reasons for ineligibility were ECOG performance score more than 1 (n=23), comorbidities (n=18), not R/R to two prior lines of therapy (LOT) (n=15) and rapid disease progression (n=15). Prohibitive comorbidities included: creatinine clearance <45ml/min (n=13), left ventricular ejection fraction <45% (n=2), unstable coronary artery disease (n=1), severe valvular disease (n=1) and Child B cirrhosis (n=1). 10 declined CAR-T and 10 were diagnosed or had lymphoma subtypes not covered by CAR-T reimbursement criteria: grade 3B follicular lymphoma (n=5), T-cell lymphoma (n=2), Hodgkin lymphoma (n=1), Richter from chronic lymphocytic leukemia (n=1) and transformed marginal zone lymphoma (n=1). 33 had more than one exclusion criteria. Median age at referral was 66 years (range: 25-87). Median IPI at diagnosis (available in 74%) was 3 (range: 0-5). At CAR-T evaluation, 77 patients had a stage 3 or 4 disease and 7 had CNS involvement. Median LOT for LBCL were 2 (range: 0-5), 46 were primary refractory and 23 relapsed within 12 months. 18 patients had undergone prior high dose therapy and autologous stem cell transplant (HDT-ASCT). 6 were exposed to novel therapies (polatuzumab=6, mosunetuzumab=2). Median follow-up after CAR-T exclusion was 4.25 months (range: 0-49.2). 50 (68% of patients with B-cell lymphoma R/R to at least 2 LOT) were deceased at time of analysis. Data on further LOT was available for 22 patients: 10 received novel therapies (tafasitamab=5, polatuzumab=3, mosunetuzumab=1, alectinib=1), 6 HDT-ASCT, 3 allogeneic stem cell transplant, 4 conventional chemotherapies and 2 radiation therapy. Conclusions: 39% of evaluated patients with R/R LBCL were ineligible for CAR-T mainly due to poor performance status, comorbidities and prohibitive progressive disease. Our study did not capture patients not referred due to geographical considerations but highlights dismal outcomes for patients ineligible for CAR-T. Widespread access to novel therapies is awaited.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,004 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 tête enseignante, 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 ».