A phase 2 expanded access study of zanubrutinib (ZANU) in patients (pts) with Waldenström Macroglobulinemia (WM).
Notice bibliographique
Résumé
e19522 Background: Bruton tyrosine kinase (BTK) inhibition is an emerging standard of care for WM. The next-generation BTK inhibitor ZANU (BGB-3111), designed to maximize BTK occupancy and minimize off-target inhibition of other kinases, is approved by the United States (US) Food and Drug Administration, Health Canada, and the European Union at a dose of 320 mg once daily (QD) or 160 mg twice daily (BID) for adult pts with WM. BGB-3111-216 is a single-arm expanded access study of ZANU in treatment-naïve (TN) pts who were unsuitable for standard chemoimmunotherapy or pts with relapsed refractory (R/R) WM. This study provides real-world experience with ZANU in pts with WM. Methods: Eligible pts with TN or R/R WM received ZANU 320 mg QD or 160 mg BID orally. Primary endpoint was the number of pts enrolled/treated and enrolling sites. Secondary endpoints included treatment-emergent adverse events (TEAEs) of special interest, disease response rate, progression-free survival (PFS), and overall survival (OS). Response was evaluated by investigator assessment according to the 6th International Workshop on WM ( Br J Haematol. 2013;160(2):171-6) every 6 mo at minimum. The study was closed by the sponsor in July 2021 and active pts were transitioned to commercial ZANU via a patient assistance program. Results: Fifty pts with WM (17, TN; 33, R/R) were enrolled between December 2019 and June 2021 across 10 academic and community medical centers in the US. Median age was 72 years, 54% had intermediate-, 40% had high-risk disease, and the median number of prior therapies for R/R pts was 2. Median treatment exposure was 9.2 mo (range, 1.4-20.0). Thirty-eight (76%) pts had ≥1 TEAE, and 36 (72%) had ≥1 TEAE of special interest. Grade ≥3 TEAEs of special interest were hypertension (8%), infection (8%), atrial fibrillation/flutter (2%), neutropenia (2%), and second primary malignancy (2%). No new safety signals were observed. In pts with ≥1 response evaluation, 39% achieved a best overall response (BOR) of very good partial response. Overall response rate was 85.4% and major response rate was 73.2% (Table). Of the 4 pts with BOR of progressive disease, 3 had IgM values that met partial response criteria before the 6-mo response assessment. PFS and OS were immature due to short follow-up, and the median was not met. Conclusions: These real-world expanded access study results were consistent with the established ZANU profile in WM or other B-cell malignancies when administered as oral monotherapy at 160 mg BID or 320 mg QD in pts with intermediate or high-risk R/R or TN WM. Clinical trial information: NCT04052854. [Table: see text]
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 | 0,004 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 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 | 0,001 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,002 |
| 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 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 ».