P908: IDENTIFICATION OF CYTOKINES ASSOCIATED WITH RESPONSE AND CYTOKINE RELEASE SYNDROME – ANALYSIS OF MAGNETISMM-3 COHORT A
Notice bibliographique
Résumé
Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: MagnetisMM-3 (NCT04649359) is a phase 2 study of elranatamab monotherapy in patients with multiple myeloma refractory to at least 1 proteasome inhibitor, 1 immunomodulatory drug, and 1 anti-CD38 antibody. Promising efficacy and safety have been observed in patients who were naïve to B-cell maturation antigen (BCMA)-directed therapy (Cohort A) in MagnetisMM-3 (Bahlis et al., ASH 2022). Aims: This analysis examined the relationship between cytokine levels and elranatamab response, and cytokine levels and cytokine release syndrome (CRS), in BCMA-naïve patients from MagnetisMM-3. Methods: In MagnetisMM-3, patients received subcutaneous elranatamab in 28-day cycles with step-up doses of 12 mg on C1D1 and 32 mg on C1D4 followed by 76 mg QW beginning C1D8. Serum samples were collected on C1D1 prior to first priming dose, and on C1D2, pre-dose C1D4, C1D5, pre-dose C1D8, C1D15, and C1D22. Levels of 45 peripheral cytokines were analyzed by proximity extension assay and a longitudinal mixed effects model was applied to each cytokine separately. Cytokines with a significant 2-fold differential expression in responders (defined as patients with best overall response of very good partial response [VGPR] or better) vs non-responders (defined as patients with best overall response of partial response or worse) and in patients with CRS vs no CRS at any timepoint are reported. Clinical data cutoff was Oct 2022 with a median follow up of 10.4 months. Results: Baseline levels of IL-6 (2.6-fold), IL-17C (2.0-fold), and MIP-1α (2.1-fold) were lower in patients who achieved a response. After the first priming dose, 13 cytokines in the panel, including CCL8, IFN-γ, IL-2, and IL-27, were differentially expressed in responders vs non-responders. At baseline, no cytokines were found to predict CRS. After the first priming dose, 18 cytokines in the panel, including CCL8, IFN-γ, IL-10, IL-2, IL-27, IL-6 (Figure), and IL-17A, were differentially expressed in patients with CRS vs no CRS. The maximal differential expression for 17/18 cytokines occurred at C1D2, ~24 hours post the first priming dose. Summary/Conclusion: Lower baseline levels of IL-6, IL-17C, and MIP-1α correlated with a response of VGPR or better in BCMA-naïve patients from MagnetisMM-3, suggesting that lower levels of these cytokines might reflect a favorable immune environment. Many cytokines were differentially expressed at higher levels in patients who experienced CRS vs those who did not; the most prominent cytokines included CCL-8, IFN-γ, and IL-10. The timing of induction of CCL-8, IFN-γ, and IL-10 occurred by C1D2 suggesting a potential contribution of these cytokines in driving CRS.Keywords: Cytokine, Clinical trial, Multiple myeloma, Myeloma
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 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 | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 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) | 0,000 | 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 découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, 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 ».