Once weekly selinexor, carfilzomib, and dexamethasone (XKd) in carfilzomib nonrefractory multiple myeloma (MM) patients.
Notice bibliographique
Résumé
8038 Background: Exportin 1 (XPO1) mediates the nuclear export and functional inactivation of tumor suppressor proteins (TSPs), is associated with poor prognosis in MM, and contributes to proteasome inhibitor (PI) and immunomodulatory drug (IMiD) resistance. Selinexor (SEL) is a novel, oral, first-in-class selective inhibitor of nuclear export (SINE) compound that blocks XPO1, forcing the nuclear retention and activation of TSPs. SEL in combination with low dose dexamethasone (dex) ± bortezomib (BOR) is FDA approved for previously treated MM. The synergy of SEL with the PI BOR has been confirmed in the phase 3 BOSTON study in MM patients (pts) with 1-3 prior therapies; once weekly (QW) SEL, QW BOR, and dex (XVd) significantly increased progression-free survival (PFS), time to next therapy, and overall response rate (ORR) as compared to standard twice weekly BOR/dex (Vd), despite XVd using 40% less BOR and 25% less dex than standard Vd. We hypothesized that the addition of QW SEL to the PI carfilzomib (CAR)-dex (XKd) would be an active and tolerable regimen in pts with heavily pretreated MM. Methods: In the XKd arm of the multi-arm Phase 1b/2 STOMP study, SEL at 80 or 100 mg QW was evaluated in combination with CAR at 56 or 70 mg/m2 QW plus dex at 40 mg QW in pts with heavily pretreated MM not refractory to CAR. Study objectives were to determine the maximum tolerated dose and recommended phase 2 dose (RP2D) and assess the safety and activity of the XKd regimen. Results: As of 4Jan2021, 27 pts were enrolled: 18 (67%) were male, median age 71 years (range 50-76), and median of 4 (range 1-8) prior lines of therapy. All 27 pts were previously treated with BOR, 26 (96%) lenalidomide (LEN), 19 (70%) pomalidomide (POM), 18 (67%) daratumumab (dara). The majority (67%) of pts were triple-class pretreated (PI, IMiD, and anti-CD38 mAb), and 44% had triple-class refractory MM. Nine pts (33%) had MM quad-refractory to BOR, LEN, POM, and dara. Common hematologic treatment-related adverse events (TRAEs) (total, grade ≥3) included thrombocytopenia (74%, 56%), anemia (59%, 19%), and neutropenia (30%, 7%). Non-hematologic TRAEs included nausea (67%, 4%), fatigue (52%, 7%), and anorexia (52%, 4%). RP2D was identified as SEL 80 mg QW, CAR 56 mg/m2 QW, and dex 40 mg QW. As of 3Feb2021, ORR was 78% (21/27) with 5 pts reaching CR (19%), 8 VGPR (30%), and 8 PR (30%). Median PFS was 23.7 months. Among 18 pts pretreated with dara, ORR was 67% and median PFS 23.7 months. In 9 pts whose MM was refractory to BOR, LEN, POM, and dara, ORR was 67% with 4 VGPR (44%). Conclusions: In pts with heavily pretreated MM, weekly XKd is highly active with an ORR of 78% and deep responses (≥VGPR 48%) with an overall PFS of 23 months. All AEs including grade 3/4 thrombocytopenia can be managed with appropriate supportive care and dose modifications. These data support further investigation of XKd in pts with previously treated MM including those previously treated with dara.
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 | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».