DARATUMUMAB + BORTEZOMIB, LENALIDOMIDE, AND DEXAMETHASONE (DVRD) VS VRD IN TRANSPLANT-INELIGIBLE (TIE)/TRANSPLANT-DEFERRED (TD) NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM): PHASE 3 CEPHEUS TRIAL CYTOGENETIC SUBGROUP ANALYSIS
Notice bibliographique
Résumé
In CEPHEUS, DVRd significantly improved overall MRD negativity (MRD neg + ≥CR) and sustained MRD neg rates and PFS in patients (pts) with TIE/TD NDMM. In this post hoc analysis, we report outcomes in cytogenetic risk subgroups. To gain additional insight into those patients who had long-term clinical benefit ≥5 years after a single cilta-cel infusion, we conducted a post hoc analysis. We report OS, ≥5-year progression-free outcomes, associated biomarkers, and safety from CARTITUDE-1, with 61.3-month median follow-up. Pts with TIE/TD NDMM were randomized 1:1 to DVRd or VRd. High-risk (HiR) cytogenetic abnormalities (HRCAs) were assessed by FISH. HiR was ≥1 of: del(17p); t(4;14); t(14;16). Revised HiR (R-HiR) was ≥1 of above or gain (3 copies) or amp(1q) (≥4 copies). Standard risk (SR) was 0 HRCAs; revised SR (R-SR) was 0 revised HRCAs. Additional risk groups included: gain or amp(1q) + other HRCAs; 1 and ≥2 revised HRCAs. We assessed overall MRD neg rate, sustained MRD neg, ≥CR rate, and PFS. We reported all MRD neg rates at 10-5 unless noted. Of 395 randomized pts (DVRd, n = 197; VRd, n = 198), 298 had SR (DVRd, n = 149; VRd, n = 149) and 52 HiR (DVRd, n = 25; VRd, n = 27). 184 pts had R-SR (DVRd, n = 94; VRd, n = 90) and 167 R-HiR (DVRd, n = 83; VRd, n = 84). At median 58.7-month (mo) follow-up, overall MRD neg rate was higher with DVRd vs VRd in SR (64% vs 38%; P < 0.0001) and R-SR pts (68% vs 38%; P < 0.0001). Rates by treatment (tx) arm in HiR (48% vs 56%; P = 0.7816) and R-HiR pts (55% vs 45%; P = 0.2169) were comparable. DVRd improved ≥1-year (y) sustained MRD neg rate vs VRd in SR (51% vs 26%; P < 0.0001) and R-SR pts (54% vs 24%; P < 0.0001). Sustained MRD neg rates by tx arm were comparable in HiR (40% vs 37%; P = 1.0000) and R-HiR pts (43% vs 30%; P = 0.0782). PFS was improved with DVRd vs VRd in SR (HR = 0.61 [95% CI, 0.41–0.91]; P = 0.01) and R-SR (HR = 0.54 [95% CI, 0.32–0.91]; P = 0.01) pts and was comparable by tx arm in HiR (HR = 0.88 [95% CI, 0.48–1.84]; P = 0.73); and R-HiR HR = 0.73[95% CI, 0.46–1.15]; P = 0.17; pts (), including in MRD neg pts (R-SR: (HR = 0.63 [95% CI, 0.26–1.52]; P = 0.30); R-HiR: HR = 0.71 [95% CI, 0.32–1.58]; P = 0.39. Gain(1q)+otherHRCAs HR = 0.80[95% CI, 0.45–1.42]; P = 0.044; Amp(1q)+other HRCAs HR = 0.97 [95% CI, 0.38–2.47]; P = 0.95. 1 revised HRCA HR = 0.63[95% CI, 0.37–1.09]; P = 0.09; ≥2 revised HRCA (HR = 1.01[95% CI, 0.42–2.44]; P = 0.98) Remaining outcomes, including rates of ≥CR, ≥2-y sustained MRD neg, and overall and ≥1-y sustained MRD neg at 10-6, were improved with DVRd in SR and R-SR pts and comparable by tx arm in HiR and R-HiR pts. In CEPHEUS, DVRd consistently improved the key response outcomes of MRD neg and PFS in (R-)SR pts. In HiR pts, MRD and PFS outcomes trended lower in both tx arms vs those in SR pts. Here, DVRd mostly improved PFS outcomes vs VRd; however, pt numbers were small, with the study underpowered for HiR pts. These data support use of DVRd for TIE/TD NDMM regardless of cytogenetic risk status. This study was funded by Johnson & Johnson. Medical writing support was provided by Maggie Hartman, PharmD, of Eloquent Scientific Solutions, and funded by Johnson & Johnson.
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 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 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 ».