Delayed immune-related adverse events in patients with advanced melanoma treated with immune checkpoint inhibitors.
Notice bibliographique
Résumé
12047 Background: Immune checkpoint inhibitors (ICIs) have changed the treatment landscape of melanoma but can have serious or life-altering immune-related adverse events (irAEs). Most toxicities associated with ICIs occur within the first few months (mo) of treatment initiation, but delayed irAEs occurring 12 mo after ICI start are not well characterized. Further, clinical trials often have limited follow-up of AEs and thus, real world data is valuable. Methods: Patients (pts) ≥18 years with advanced melanoma who received ≥1 cycle of an ICI at BC Cancer from 2012-2019 with ≥12 mo of follow-up from time of ICI initiation were identified using the BC Cancer Registry and Pharmacy databases. Data on baseline clinicopathologic factors prior to the first cycle of ICI, and delayed irAE history and management were extracted. Delayed irAEs were graded using CTCAEv5. Results: In total, 530 pts treated with ≥1 cycle of an ICI were identified of which 309 pts had ≥12 mo of follow-up. Median follow-up for alive pts was 65.3 mo (13.0-143.5 mo). 96 (31%), 147 (48%), 19 (6%), and 47 (15%) pts received combination ICI (nivolumab/ipilimumab ± nivolumab maintenance), PD-1 inhibitor monotherapy (nivolumab or pembrolizumab), CTLA-4 inhibitor monotherapy (ipilimumab), and sequential CTLA-4 and PD-1 inhibitors, respectively. A total of 142 delayed irAEs were recorded in 94 (30%) pts. Median time to onset of delayed irAEs was 20.0 mo (12.2-80.6 mo). The most common delayed irAEs were dermatologic (27%), gastrointestinal (23%), and rheumatologic (20%). Most delayed irAEs were grade ≤2 (84%), but some were grade ≥3 (16%). Of individual delayed irAEs, 75 (51%) occurred on ICI treatment at time of onset, 39 (26%) after ≤3 mo of the last ICI cycle, and 34 (23%) after >3 mo of the last ICI cycle. 79 (56%) and 20 (14%) delayed irAEs were treated with systemic steroids and immunomodulators, respectively. Further, 12 (8%) delayed irAEs led to hospitalization, and 64 (45%) required subspecialty consultation. Pts with a history of autoimmune disease were more likely to have a delayed irAE (p=0.02), as were pts who achieved a partial or complete response (p=0.02). There was a trend towards a greater frequency of delayed irAEs in pts treated with PD-1 (37%) compared with combination (28%), CTLA-4 (11%), or sequential CTLA-4 and PD-1 (28%) (p=0.068). Conclusions: Delayed irAEs occurred in almost a third of pts with advanced melanoma treated with ICIs and followed for at least 1 year. Extended follow-up to monitor for delayed irAEs should be considered as many events required immunosuppressive therapy and rarely, may be life threatening. [Table: see text]
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 | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,001 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».