JAK inhibitor for the treatment of steroid refractory and life-threatening immune-related adverse events secondary to immune checkpoint inhibitors.
Notice bibliographique
Résumé
2643 Background: Immune checkpoint inhibitors (ICIs) boost anti-tumor immune responses but carry the risk of off-target effects, manifesting as immune-related adverse events (irAEs). Approximately 20% of irAEs are refractory to steroids, requiring subsequent immunosuppressive therapies, while a smaller subset presents with fulminant reactions requiring multiple agents simultaneously. Although biologics like TNF and IL-6 inhibitors are often used, their targeting of single inflammatory pathways may be insufficient to resolve irAEs in these critical scenarios. We conducted a prospective study to assess the safety and efficacy of oral JAK inhibitors, molecules capable of rapidly modulating multiple inflammatory cytokine signals, in managing steroid-refractory or life-threatening irAEs. Methods: The MIRAE Biobank is a prospective cohort study of cancer patients treated with ICI at the Jewish General Hospital in Montreal, Canada. Patients with steroid refractory subjects with grade > 3 irAE or persistent grade 2 toxicity despite optimal therapy, as well as life-threatening irAEs in the first-line setting treated with JAK inhibitors were extracted from the database and their clinical data was summarized. Among those who survived at least 30 days post-JAK inhibitor, we compared characteristics of responders and non-responders. Responders were defined as resolution of the irAE to grade < 1 and < 10mg prednisone equivalents without any relapses during a 30-day period. Results: In this series, 29 patients were treated with JAK inhibitors for refractory or life-threatening irAEs. Mean age was 69 years, 34.5% were women, 82.8% received anti-programmed cell death protein-1 (PD-1) antibodies alone, and 13.8% patients were treated with the combination of anti-cytotoxic T lymphocyte antigen-4 and anti-PD-1 antibodies. Cancer types were primarily melanoma (10, 34.5%) and lung cancer (6, 20.7%). Primary irAEs for which JAK inhibitors were initiated included myocarditis (n=11), colitis (n=4), arthritis (n=4), hepatitis (n=4), encephalitis (n=2), pneumonitis (n=2), myasthenia gravis (n=1) and sicca (n=1). JAK inhibitors were used as second- (refractory to steroids alone), third- or fourth- or more line in 9, 11 and 9 patients, respectively. Median duration of JAK inhibitor exposure was 30.5 days. Among the 24 patients who survived at least 30 days, 17 (71%) responded after a median of 11 days from initiation of the JAK inhibitor. Interestingly, this included 6/8 patients with myocarditis, 4/4 with arthritis and 2/3 with colitis. Of those who responded to JAK inhibitor, 11/18 were steroid refractory and 6/6 were life-threatening cases requiring simultaneous treatment with steroids. Conclusions: This preliminary data suggests that JAK inhibitors may be effective at treating various types of steroid-refractory and life-threatening irAEs.
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 | 0,000 |
| 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) | 0,005 | 0,001 |
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 ».