INTEGRATED ANALYSIS: OUTCOMES OF IBRUTINIB‐TREATED PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LEUKEMIA (CLL/SLL) WITH HIGH‐RISK PROGNOSTIC FACTORS
Notice bibliographique
Résumé
Introduction: In phase 3 studies, ibrutinib (ibr) was superior to ofatumumab in relapsed/refractory (R/R) CLL/SLL or chlorambucil in treatment (tx)-naïve (TN) CLL/SLL. Ibr + bendamustine/rituximab (BR) was superior to BR in R/R CLL/SLL. Clinical outcomes of pts in these 3 studies were examined to determine the impact of certain prognostic risk factors other than del17p. Methods: RESONATE: R/R CLL/SLL, ibr 420 mg/d until progressive disease (PD) or ofatumumab (≤24 wk). RESONATE-2: TN CLL/SLL (no del17p) ≥65 y, ibr 420 mg/d until PD or chlorambucil (≤12 cycles). HELIOS: R/R CLL/SLL (no del17p), BR (≤6 cycles) ± ibr 420 mg/d followed by ibr or placebo until PD. Data from 3 studies (N = 1238) were pooled to analyze outcomes with/without genomic risk factors IGHV, del11q, trisomy 12, or complex karyotype (CK). Covariates for a multivariate analysis (MVA) for progression-free and overall survival (PFS, OS): the 4 genomic risk factors, age, sex, ECOG PS, cytopenias, LDH, bulky disease, and number of prior therapies. Results: Median follow-up was 21 mo for both ibr- and comparator-tx pts. In each subgroup, PFS, OS, and response rates were higher in ibr- than comparator-tx pts, regardless of these genomic risk factors. By univariate analysis (UVA, Table) in ibr-tx pts, genomic risk factors were not associated with shorter PFS or OS, and del11q was associated with a trend of longer PFS and OS. In comparator-tx pts, unmutated (U)-IGHV, del11q, and CK were associated with shorter PFS, and U-IGHV and CK with shorter OS. By MVA for PFS/OS, in ibr-tx pts (without del17p), only ≥1 prior tx was associated with shorter PFS and OS. Age ≥ 65 and elevated LDH were associated with shorter OS, and del11q with a trend of longer OS. In comparator-tx pts, ≥1 prior tx, U-IGHV, del11q, CK, male sex, and bulky disease ≥5 cm were associated with shorter PFS; CK, male sex, bulky disease ≥5 cm, ECOG PS ≥1 and elevated LDH were associated with shorter OS. Cumulative rates of adverse events were similar in pts with/without genomic factors and reflect a median exposure of 19-20 mo for ibr-tx pts and 5-10 mo for comparator-tx pts. Conclusions: In UVA and MVA for ibr-tx pts, no clear associations were found for U-IGHV, del11q, trisomy 12, and CK with poor outcomes; del11q associated with trends of longer PFS and OS in UVA, and longer OS in MVA. In comparator-tx pts, U-IGHV, del11q, and CK associated with shorter PFS, OS, and/or lower response rate. Results suggest that risk factors associated with poor outcomes with chemotherapy have less relevance with ibr. CRR, complete response rate; HR, hazard ratio; NE, not evaluable; OR, odds ratio; ORR, overall response rate. *For IGHV, indicates mutated IGHV. **18 mo PFS rate was 8%. Keywords: chronic lymphocytic leukemia (CLL); ibrutinib; small lymphocytic lymphoma (SLL).
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 | 0,003 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,004 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| 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 ».