Association of Immune-Related Adverse Events, Hospitalization, and Therapy Resumption With Survival Among Patients With Metastatic Melanoma Receiving Single-Agent or Combination Immunotherapy
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Notice bibliographique
Résumé
Importance: Immune-related adverse events (irAEs) due to immune checkpoint blockade (ICB) have been shown to be positively associated with survival. Among patients with metastatic melanoma, evidence supporting this association has been conflicting, while ipilimumab-nivolumab combination ICB has been examined only in small clinical cohorts. Objective: To examine the association between irAEs and survival among patients with metastatic melanoma, in particular for those receiving combination ICB. Design, Setting, and Participants: A retrospective cohort of 492 consecutive patients with metastatic melanoma treated with ICB at 2 tertiary and 4 regional cancer centers in Alberta, Canada, from August 1, 2013, to May 31, 2020, was observed. Patients were aged 18 years or older with metastatic melanoma agnostic to primary site, who received 1 or more doses of an anti-programmed cell death protein 1 agent as single or combination ICB. Clinically significant irAEs requiring systemic corticosteroids and/or treatment delay were captured. To minimize immortal time bias, only patients surviving 12 weeks after ICB initiation were included in survival analyses. Statistical analysis was conducted on December 10, 2021. Exposures: Development of irAEs requiring systemic corticosteroids and/or treatment delay. Main Outcomes and Measures: The primary outcome was overall survival (OS), with the association of irAE development with OS assessed via Kaplan-Meier and Cox proportional hazards regression analyses. The association of hospitalization for irAEs and ICB resumption after irAE with OS was examined. Results: Among 492 patients, the median age of those with irAEs was 61.8 years (IQR, 52.9-72.1 years), and the median age of those without irAEs was 65.5 years (IQR, 56.5-76.9 years), while sex distribution was comparable (137 of 198 men [69.2%] with irAEs vs 183 of 294 men [62.2%] without irAEs). There was an association between irAEs and OS both in the overall cohort (with irAEs: median OS, 56.3 months [95% CI, 38.2 months to not evaluable] vs without irAEs: median OS, 18.5 months [95% CI, 14.4-23.2 months]; P < .001) and in the 124 patients (25.2%) receiving combination ICB (with irAEs: median OS, 56.2 months [95% CI, 52.2 months to not evaluable] vs without irAEs: median OS, 19.0 months [95% CI, 6.6 months to not evaluable]; P < .001). Hospitalization for irAE did not alter this positive association with OS compared with outpatient treatment (median OS, not evaluable [95% CI, 31.5 months to not evaluable] vs median OS, 52.2 months [95% CI, 35.2 months to not evaluable]; P = .53), while resumption of ICB was associated with longer OS than not resuming ICB (median, 56.3 months [95% CI, 40.8 months to not evaluable] vs 31.5 months [95% CI, 21.0 months to not evaluable]; P = .009). A favorable independent association of irAEs with OS was confirmed in multivariable analysis (hazard ratio for death, 0.382 [95% CI, 0.254-0.576]; P < .001). Conclusions and Relevance: This study suggests an association between irAEs and OS for patients with metastatic melanoma, including those treated with combination ICB and those with severe irAEs requiring hospitalization. The potential benefit associated with ICB resumption after irAEs warrants further investigation.
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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 | 0,002 | 0,000 |
| 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) | 0,000 | 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 découle