Anti-PD1-Induced Immune-Related Adverse Events and Survival Outcomes in Advanced Melanoma
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Résumé
INTRODUCTION: Objective response rates (ORR) appear to be higher in melanoma patients who develop immune-related adverse events (irAEs), but whether there is a similar association between irAEs and survival remains unknown. MATERIALS AND METHODS: Patients with advanced melanoma treated with single-agent pembrolizumab or nivolumab in the province of Alberta from June 2014 to May 2017 were identified through the provincial pharmacy database. Chart review identified and categorized all irAEs that occurred while on anti-programmed cell death protein 1 (PD-1) checkpoint inhibitors. The primary objective was to compare overall survival (OS) with patients who developed any irAEs versus those who did not. Secondary outcomes included progression-free survival (PFS) and ORR. RESULTS: Among 186 patients, any-grade and grade ≥3 irAEs occurred in 88 (47%) and 27 (15%) patients, respectively; one patient died of pneumonitis. In a landmark analysis excluding patients who died within the first 12 weeks, the median follow-up was 24 months, 20 months in patients without any irAEs and 26 months in patients with irAEs (p = .006). Median OS was 39 versus 23 months (hazard ratio [HR], 0.46; p = .001) for any irAE and no irAE, respectively, and median OS not reached versus 29 months for grade ≥3 irAEs and no grade ≥3 irAEs, respectively. In multivariate analysis, elevated lactate dehydrogenase correlated with reduced OS (HR, 2.34; p = .001), whereas each additional cycle of treatment received (HR, 0.94; p < .001) and development of grade ≥3 irAEs (HR, 0.29, p = .024) were significantly associated with longer OS. CONCLUSION: Anti-PD-1-associated grade ≥3 irAEs in patients with advanced melanoma is associated with better patient outcomes, including overall survival. IMPLICATIONS FOR PRACTICE: Previous prospective randomized clinical trials demonstrate improved response rates in patients with melanoma who develop select adverse events. The current population-based real-world study in advanced melanoma reports an association with anti-programmed cell death protein 1 (PD-1)-induced grade ≥3 immune-related adverse events (irAEs) and better patient outcomes, including overall survival. These results suggest that irAEs may be a manifestation of a patient's ability to mount a systemic immune response from PD-1-directed therapies, which may be associated with therapeutic benefit. The finding of irAEs coinciding with clinical benefit from these therapies supposes that these events are, by and large, unavoidable, and the critical management of irAEs remains essential for optimizing patient outcomes.
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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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| 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