PHASE 1B KEYNOTE‐013 STUDY OF PEMBROLIZUMAB IN PATIENTS WITH CLASSIC HODGKIN LYMPHOMA AFTER BRENTUXIMAB VEDOTIN FAILURE: RESULTS OF >4 YEARS OF FOLLOW‐UP
Notice bibliographique
Résumé
Introduction: Programmed death-1 (PD-1) inhibitors are an effective treatment option for patients (pts) with relapsed/refractory classic Hodgkin lymphoma (cHL). The multicohort phase 1b KEYNOTE-013 study (NCT01953692) of the PD-1 inhibitor pembrolizumab (pembro) in pts with hematologic malignancies included cHL as an independent expansion cohort. To better understand the durability of responses in this patient population, we present long-term follow-up results for the cHL cohort. Methods: Pts with cHL who experienced relapse after, were ineligible for or refused autologous stem cell transplantation (ASCT) and whose disease progressed after brentuximab vedotin (BV) therapy were enrolled. Pts received pembro IV 10 mg/kg every 2 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Primary end points were safety and complete remission rate (CRR) per central review. Secondary end points were overall response rate (ORR) duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Data cutoff was September 28, 2018. Results: Among enrolled patients (N = 31), median follow-up was 52.8 mo (range, 7.0-57.6).The median number of lines of prior therapy was 5 (range, 2-15), and in 74% of pts, prior ASCT was ineffective. At analysis, 81% of pts had discontinued, primarily because of progression (48%), and 19% of pts had completed treatment. CRR was 19% and partial remission was 39%; ORR was 58% (18/31) (Table). Median DOR was not reached (Figure). Seven patients had a response duration ≥12 mo; 2 patients had a response duration ≥36 mo. Median PFS was 11.4 mo (95% CI, 4.9-27.8); 24-mo PFS rate was 30% (Figure). Median OS was not reached; 24-mo and 36-mo OS rates were 87% and 81%, respectively. Among pts refractory to (n = 11) and not refractory to (n = 20) first treatment, CRR was 27% and 15% respectively; ORR was 55% and 60%. By transplant status and BV status at baseline, ORR was 69% among pts who received BV after ASCT failure, 57% among pts with failed ASCT and BV before ASCT and 38% among pts who received BV and were ineligible for ASCT (Table). Overall, 22 pts (71%) experienced treatment-related adverse events (TRAEs), with diarrhea (23%) the most common; 6 pts (19%) experienced grade 3-5 TRAEs. Conclusions: After a median follow-up of >4 years, some heavily pretreated pts for whom BV therapy was ineffective maintained long-term response with single-agent pembro. The safety profile of pembro was tolerable and as expected. Keywords: Hodgkin lymphoma (HL); PD-1; Pembrolizumab. Disclosures: Zinzani, P: Consultant Advisory Role: Verastem, MSD, Eusapharma, Sanofi, Celltrion, Gilead, Janssen-Cilag, BMS, Servier, Sandoz, Immune Design, Celgene, Portola, Roche, Kyowa Kirin; Other Remuneration: Speaker's Bureau: Verastem, Celltrion, Gilead, Janssen-Cilag, BMS, Servier, MSD, Immune Design, Celgene, Portola, Roche, Eusapharma, Kyowa Kirin. Armand, P: Employment Leadership Position: Merck & Co., Inc., Bristol Myers Squibb Pharmaceuticals, Infinity Pharmaceuticals; Consultant Advisory Role: Merck & Co., Bristol Myers Squibb Pharmaceuticals, Infinity Pharmaceuticals; Research Funding: Merck & Co., Bristol Myers Squibb Pharmaceuticals, Pfizer, Inc, Affimed, Roche, Serventa, Otsuka, Sigma-Tau; Other Remuneration: Travel fees, gifts, and others: Bristol Myers Squibb Pharmaceuticals, Merck & Co.. Ribrag, V: Employment Leadership Position: Gilead, Infinity, Bristol Myers Squibb Pharmaceuticals, Laboratoires Servier, NanoString Technologies, Incyte Corporation; Consultant Advisory Role: Gilead, Infinity, Bristol Myers Squibb Pharmaceuticals, Laboratoires Servier, NanoString Technologies, Incyte Corporation; Research Funding: Amgen; Other Remuneration: Travel fees, gifts, and others: Roche, Bristol Myers Squibb Pharmaceuticals. Kuruvilla, J: Consultant Advisory Role: Merck; Other Remuneration: Payment for lectures including service on speaker's bureau: Merck. Zhu, Y: Employment Leadership Position: Merck. Farooqui, M: Employment Leadership Position: Merck & Co., Inc.; Stock Ownership: Merck & Co., Inc. Nahar, A: Employment Leadership Position: Merck & Co., Inc. Moskowitz, C: Employment Leadership Position: Celgene, Genentech, Merck & Co., Seattle Genetics Inc.; Consultant Advisory Role: Celgene, Genentech, Merck & Co., Seattle Genetics Inc.; Research Funding: Pharmacyclics, Genentech, Merck & Co., Seattle Genetics Inc.
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) | 0,002 | 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 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 ».