Safety and efficacy of tisagenlecleucel (tisa-cel) plus pembrolizumab (pembro) in patients (pts) with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL): Updated analysis of the phase 1b PORTIA study.
Notice bibliographique
Résumé
e19537 Background: Tisa-cel showed durable responses and manageable safety in pts with r/r DLBCL in the phase 2 JULIET trial. High baseline programmed cell death 1 (PD-1) expression associated with higher probability of no response (Schuster et al. NEJM 2019). Here we report an updated analysis of PORTIA, a phase 1b, multicenter, open-label study of tisa-cel plus pembro in pts with r/r DLBCL. Methods: Eligible pts (≥18 y) had r/r DLBCL after ≥2 lines of therapy and relapsed after or were not candidates for autologous stem cell transplant (autoSCT). Patients received a single tisa-cel infusion on Day 1 and were enrolled in 1 of 3 cohorts that initiated pembro (200 mg q 21 days, for up to 6 doses) on either Days +15, +8, or –1. Primary endpoints were incidence of dose-limiting toxicities (DLTs) and overall response rate (ORR; complete response [CR] and partial response [PR]). Secondary endpoints included duration of response, progression-free survival, overall survival, safety, and cellular kinetics. Results: As of November 9, 2020, 15 pts were enrolled and 12 received tisa-cel (n = 4 pts for each Days +15, +8, and –1 cohorts; median follow-up, 4 mo). At study entry, the median age among treated pts was 62 y (range, 35-79), 100% had an International Prognostic Index score ≥2, 67% had ≥3 prior lines of therapy, 58% had stage IV disease, 58% had lactate dehydrogenase > ULN, and 42% had prior autoSCT. All 12 pts had ≥1 AE. Grade ≥3 AEs suspected to be related to tisa-cel and/or pembro were neutropenia (n = 4); neutrophil count decreased (n = 3); febrile neutropenia, lymphocyte count decreased, malnutrition (each n = 2); anemia, leukopenia, diarrhea, white blood count decreased, liver function tests increased, thrombocytopenia, hepatitis, and cytokine release syndrome (CRS; each n = 1). No neurotoxicity or DLTs were observed. Among the Day +15, +8, and –1 cohorts (each n = 4), the ORR was 50% (2/4; CR n = 0, PR n = 2), 25% (1/4; CR n = 1, PR n = 0), and 25% (1/4; CR n = 1, PR n = 0; longer follow-up is needed for n = 2 pts), respectively. Tisa-cel exposure and peak expansion were consistent with JULIET, with a trend toward delayed expansion in the Day –1 cohort (n = 4). There was no sign of secondary expansion following pembro administration regardless of the number of doses. Compared with JULIET, lower CRS severity and frequency and lower cytokine profiles were observed for all 3 cohorts. Conclusions: The combination of tisa-cel plus pembro was feasible and showed manageable safety. The lack of improved efficacy in PORTIA with the addition of pembro compared with tisa-cel alone may be related to more pts with ≥3 prior lines of therapy (67% vs 51%, respectively), and/or pts with more advanced disease in PORTIA. Additional studies with larger patient cohorts are needed to determine the value of adding PD-1 inhibitors to CAR-T cell therapy in pts with r/r DLBCL. Clinical trial information: NCT03630159.
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 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 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 | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 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 ».