Long-term toxicities with immune checkpoint inhibitor (ICI) in melanoma patients.
Notice bibliographique
Résumé
e21549 Background: The incorporation of ICI into the treatment of melanoma has greatly improved patient outcomes, but this benefit has come at the cost of exposing patients to immune-related adverse events (irAEs). A wide spectrum of irAE types has been described, and severity is known to vary from minor to life-threatening; however, the literature to date on the chronicity of irAEs is limited. Objectives: To characterize the long-term and permanent irAEs associated with ICI treatment in patients with melanoma, the treatment of irAEs and the association with survival outcomes. Methods: We performed a retrospective chart review of 161 adult patients with melanoma treated with at least one cycle of ICI regimen in the adjuvant or metastatic setting: 129 patients received PD-1 inhibitor monotherapy and 32 received dual immunotherapy. Patients were grouped by duration of irAE: permanent (no complete resolution), long-term (resolution over a period ≥6 months), transient (resolution over a period < 6 months), or no irAEs. Overall survival was evaluated for those patients that were treated in the metastatic setting with PD1 inhibitor monotherapy. Results: Thirty-eight patients were treated in the adjuvant setting and 123 patients were treated in the metastatic setting. A total of 279 irAEs were reported in the whole patient population. Sixty-six (41.0%) patients developed permanent irAEs, 15 (9.3%) experienced long-term irAEs as their longest-lasting toxicity, 34 (21.1%) developed transient irAEs only, and 46 (28.6%) experienced no irAEs. Permanent irAEs occurred in 21 (65.6%) patients treated with dual immunotherapy and in 45 (34.9%) patients treated with monotherapy. The majority of permanent irAEs were endocrine-related (35.5%) or skin-related (32.7%). Grade ≥3 permanent irAEs occurred in 20 (12.4%) patients and included toxicities such as adrenal insufficiency, myocarditis, and myelitis. Fifty-three (32.9%) patients were still on treatment for long-term or permanent irAEs 6 months or more following completion of ICI therapy, including 23 patients on thyroid replacement and 22 on oral steroids. ICI treatment was temporarily interrupted for 63 (22.6%) irAEs and permanently discontinued due to irAE in 38 (13.6%) patients. Subgroup analysis of patients who received single-agent ICI in the first-line palliative setting reveals that those with longer-duration irAEs had a significantly longer median overall survival. Conclusions: Despite the significant benefits, treatment with ICIs in melanoma is associated with a wide range of toxicities that can be permanent and may have long-lasting impacts on patients. The risk of long-term toxicity should therefore be discussed when obtaining consent for treatment. As these treatments are being used more commonly in the adjuvant setting, the impact of survivorship and the long-term management of these toxicities is increasingly important.
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 | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| 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) | 0,001 | 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 ».