P1067: ESTIMATING THE RELATIVE EFFICACY OF FAVEZELIMAB WHEN USED IN COMBINATION WITH PEMBROLIZUMAB IN PATIENTS WITH PD-1–REFRACTORY CLASSICAL HODGKIN LYMPHOMA
Notice bibliographique
Résumé
Topic: 17. Hodgkin lymphoma - Clinical Background: Treatment options are limited for patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) whose disease has progressed after a PD-1 inhibitor. LAG-3 is an inhibitory receptor involved in T-cell regulation that is coexpressed with PD-1 on tumor-infiltrating T cells. Favezelimab is a LAG-3 inhibitor that showed promising antitumor activity when used in combination with the PD-1 inhibitor pembrolizumab in patients with PD-1–refractory R/R cHL in the phase 1/2 MK-4280-003 study (Timmerman J et al. J Clin Oncol. 2022;40(16 suppl):7545). Although the objective response rate (ORR) in this study was promising, the contribution of favezelimab to this response was unclear. Aims: This post hoc analysis aimed to evaluate the relative efficacy of favezelimab + pembrolizumab compared with pembrolizumab alone in patients with PD-1–refractory R/R cHL. Because no studies have investigated pembrolizumab monotherapy in this setting, historical data from patients with R/R cHL who received pembrolizumab beyond progression in the phase 2 KEYNOTE-087 study were used as a historical control. Methods: Patients from KEYNOTE-087 were included in the historical control arm if they had received more than 2 doses of pembrolizumab beyond progression, had confirmed disease progression within 12 weeks of the last dose of pembrolizumab (confirmatory scan ≥4 weeks from initial progression), and had undergone postprogression scans. All patients from MK-4280-003 with a baseline and postbaseline assessment available were included. Patients in KEYNOTE-087 received pembrolizumab 200 mg IV every 3 weeks (Q3W). Patients in MK-4280-003 received pembrolizumab 200 mg IV Q3W plus favezelimab 200 mg or 800 mg IV Q3W. For patients in the historical control arm, baseline tumor size was reset to the time of the first progression, and best change in target lesion size was calculated for the postprogression period. ORR was assessed using Cheson 2007 criteria. A bootstrapping method with 1000 samples was used to compare best change in target lesion size between the studies. Results: 27 of 33 patients enrolled in MK-4280-003 qualified for radiographic analysis and were included. In KEYNOTE-087, 123 patients developed progressive disease during treatment with pembrolizumab monotherapy, of whom 81 received postprogression pembrolizumab and were included in the historical control arm. The ORR was 31% (range, 15-51) for patients treated with favezelimab + pembrolizumab compared with 2.5% (range, 0-5.9) among patients who received pembrolizumab monotherapy beyond progression. The average response was also deeper with favezelimab + pembrolizumab compared with the historical pembrolizumab control (mean of waterfall plots, −46.6% vs −0.37%). A larger proportion of patients treated with favezelimab + pembrolizumab had a ≥50% reduction in target lesion size compared with the historical pembrolizumab control (44% vs 5%). Using the bootstrapping method, 26,826 of 27,000 (99.4%) samples showed a better response for favezelimab + pembrolizumab relative to pembrolizumab monotherapy.Summary/Conclusion: In this post hoc analysis, the combination of favezelimab + pembrolizumab was associated with a higher ORR and deeper responses than pembrolizumab monotherapy in patients with PD-1–refractory R/R cHL. Although limited by its retrospective nature, the results support the hypothesis that favezelimab contributed substantially to the efficacy observed in the MK-4280-003 study. Keywords: Clinical trial, Hodgkin’s lymphoma, Immunotherapy
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 | 0,000 |
| 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 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 ».