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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,001 |
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 source (Gemma direct ou Codex distillé), 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 ».