P490: UPDATED SURVIVAL, BLOOD COUNT RECOVERY AND SAFETY RESULTS FROM THE AGILE STUDY IN PATIENTS WITH ACUTE MYELOID LEUKEMIA TREATED WITH IVOSIDENIB + AZACITIDINE COMPARED TO PLACEBO + AZACITIDINE
Notice bibliographique
Résumé
Background: Acute myeloid leukemia (AML) is a disease with a dynamic mutational landscape; 6–10% of patients have somatic mutations in isocitrate dehydrogenase 1 (IDH1), which can drive oncogenesis. Ivosidenib (IVO) is a potent oral targeted inhibitor of mutant IDH1. In the phase 3 AGILE study in patients with newly diagnosed IDH1-mutated AML, IVO plus azacitidine (AZA) significantly improved event-free survival (EFS), overall survival (OS), complete remission (CR), and CR or CR with partial hematologic recovery (CR+CRh) rates versus placebo (PBO) plus AZA. As of March 2021, median OS (mOS) was 24 months (IVO+AZA) versus 7.9 months (PBO+AZA; HR: 0.44; one-sided p-value = 0.0005). Aims: To evaluate long-term data from AGILE on OS, transfusion independence, blood count recovery and safety in patients with newly diagnosed IDH1-mutated AML receiving IVO+AZA. Methods: In the global, phase 3, multicenter, double-blind, randomized PBO-controlled AGILE study, patients ineligible for intensive chemotherapy were randomized 1:1 to IVO 500 mg QD + AZA 75 mg/m2 SC or IV for 7 days in 28-day cycles, or PBO+AZA. Long-term follow-up data (June 2022) for OS, blood count recovery, transfusion independence and safety are described here. As of July 2021, serial bone marrow assessments were not mandated per study protocol, and therefore, updated results for the primary endpoint (EFS) are not available. Results: 148 patients were randomized: 73 to IVO+AZA; 75 to PBO+AZA. Median treatment duration was 10.8 months (IVO+AZA) versus 3.2 months (PBO+AZA). Five PBO+AZA patients crossed over to IVO+AZA after March 2021, and no adjustment was made for crossover in the updated OS analysis. At a median follow-up of 28.6 months, mOS was 29.3 months (95% CI 13.2, not reached) for IVO+AZA versus 7.9 months (95% CI 4.1, 11.3) for PBO+AZA (HR 0.42 [0.27, 0.65]; one-sided p-value <0.0001; Figure). OS rates were 62.9% and 38.3% at 12 months and 53.1% and 17.4% at 24 months, with IVO+AZA and PBO+AZA, respectively. In the IVO+AZA arm, hemoglobin levels steadily increased from baseline (BL; 88.8 g/L) to cycle 8, and then stabilized; mean platelet count recovered from BL values (72.7 x 109/L) as early as week 8 (171.9 x 109/L) and remained stable; and mean neutrophil counts rapidly increased from BL (0.98 x 109/L) to week 3 (3.99 x 109/L) and week 4 (4.36 x 109/L), and then stabilized to within the normal range. Conversion from BL transfusion dependence (red blood cell and/or platelet transfusion dependence) to post-BL transfusion independence was significantly higher with IVO+AZA than PBO+AZA (53.8% versus 17.1%, respectively; one-sided p-value = 0.0004). There were fewer neutropenic fever events (27.8% versus 33.8%) and infections (34.7% versus 51.4%) with IVO+AZA than with PBO+AZA. TEAEs led to discontinuation of IVO+AZA or PBO+AZA in 26.4% and 25.7% of patients, respectively. Summary/Conclusion: Updated data on OS (>5 months longer mOS and a greater risk reduction in deaths compared to the initial analysis), transfusion independence, blood count recovery and safety confirms the clinically and statistically robust benefit of treatment with IVO+AZA at long-term follow up. Figure: Kaplan Meier plot of OS for IVO+AZA versus PBO+AZA.Clinical trials identifier: NCT03173248. Funding: This study was supported by Agios Pharmaceuticals, Inc. Servier Pharmaceuticals LLC has completed the acquisition of Agios’ oncology business. Keywords: Acute myeloid leukemia, Hemoglobin, Platelet, Neutrophil
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 | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 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 | 0,001 |
| 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 ».