PHASE 1B STUDY OF PEMBROLIZUMAB IN PATIENTS WITH RELAPSED/REFRACTORY PRIMARY MEDIASTINAL LARGE <scp>B</scp>‐CELL LYMPHOMA (<scp>RRPMBCL</scp>): UPDATED RESULTS FROM THE <scp>KEYNOTE</scp>‐013 TRIAL
Notice bibliographique
Résumé
Introduction: Current treatments for rrPMBCL often yield poor outcomes, but PMBCL's genetics may make it susceptible to PD-1 blockade. The multicenter, multicohort KEYNOTE-013 (NCT01953692) phase 1b trial evaluates safety, tolerability, and antitumor activity of the anti-PD-1 monoclonal antibody pembrolizumab in patients (pts) with hematologic malignancies. Methods: An independent cohort of KEYNOTE-013 is enrolling PMBCL pts who relapsed after or are ineligible for autologous stem-cell transplant (SCT). Pts initially received pembrolizumab IV 10 mg/kg every 2 weeks (Q2W), later changed to an equivalent regimen of 200 mg every 3 weeks (Q3W). Treatment continues for 2 years or until unacceptable toxicity or confirmed disease progression. Treatment response is radiographically evaluated using 2007 response criteria at week 6, 12, and every 9 weeks thereafter. Primary end points were safety and objective response rate (ORR). Safety population: all pts with ≥1 dose of study drug. Efficacy population: all pts who progress prior to or reach the first efficacy evaluation. Results: By the analysis cutoff date (January 3, 2017), 22 pts had been enrolled in the PMBCL cohort, 21 were treated, and 19 were radiographically evaluable. Overall, 67% of pts had ≥3 prior lines of therapy, and 67% were ineligible for autologous SCT due to chemorefractory disease. Median follow-up duration was 14.3 months (range, 0.6 to 34.7 months). In the safety population, 14 pts (67%) experienced treatment-related adverse events (TRAEs): 4 pts with grade 3 TRAEs (neutropenia n = 2, fatigue n = 1, increased alanine aminotransferase n = 1) and 1 with a grade 4 TRAE (neutropenia). An additional patient had grade 4 venoocclusive liver disease after allogeneic SCT during the follow-up period after pembrolizumab discontinuation. Seven pts had serious AEs. There were no treatment-related deaths. In the efficacy population (19 evaluable pts and 1 with clinical progression before the first efficacy evaluation), ORR was 50%: 5 pts (25%) each achieved partial or complete response (CR). Five others (25%) had stable disease as best response. Of evaluable pts, 15 (79%) had target lesion reductions (Figure). Median duration of response (DOR) was not reached (range, 1.4 to 28.9 months); DOR in pts with CR ranged from 1.4 to 27.1 months. There were 8 ongoing responses, including 5 in pts who discontinued treatment. Seventeen pts discontinued treatment due to progressive disease on imaging (n = 7), clinical progression (n = 5), physician decision (n = 2), patient decision, CR, or AE (n = 1 each); 2 pts were discontinued after completing the maximum 2 years of treatment and remain in remission. Keywords: diffuse large B-cell lymphoma (DLBCL); non-Hodgkin lymphoma (NHL); salvage treatment
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 | 0,002 | 0,006 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 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 ».