Ibrutinib Plus Bendamustine/Rituximab (BR) Is Associated with Greater Reductions in Fatigue Than Placebo Plus BR Among Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia and Fatigue
Notice bibliographique
Résumé
Abstract Introduction: Patients with chronic lymphocytic leukemia (CLL) may have reduced health-related quality of life (HRQL) such as severe fatigue during the course of their disease and its treatment. While current treatments aim to increase progression-free survival, it is also important to maintain good HRQL for as long as possible. Methods: Ibrutinib, a first-in-class, once-daily, oral, covalent inhibitor of Bruton's tyrosine kinase, is approved in patients with previously treated CLL and in patients with CLL with del17p, and has recently been shown to reduce the risk of disease progression or death by 80% when added to standard chemoimmunotherapy with BR. In this randomized, double-blind, placebo-controlled, phase 3 study, where patients with active CLL following ≥ 1 prior therapy were randomized 1:1 to receive BR (≤ 6 cycles) with either ibrutinib (420 mg daily) (n = 289) or placebo (n = 289), HRQL and fatigue data were examined. Measures included the FACIT-Fatigue, EORTC QLQ-C30-CLL16, and EQ-5D-5L, which capture general physical and emotional impacts of disease and treatments as well as CLL-specific symptoms. Because examination of mean values may obscure meaningful changes in outcomes, fatigue scores were also examined by baseline quartile with respect to clinical, sociodemographic, and HRQL factors as well as for change over time. Individual CLL symptom items were also examined. The association between changes in hemoglobin levels and fatigue was also examined. Results: Of the 578 patients enrolled, 540 (93%) provided FACIT-Fatigue responses at baseline. No notable mean changes from baseline over time were observed in any HRQL scores within or between the treatment groups. Those in the lowest fatigue score quartile (ie, worst baseline fatigue) were more likely to have an Eastern Cooperative Oncology Group performance score of 1, be in a later stage of disease, have more cytopenias, a greater number of prior therapies, and worse HRQL. Among those with the worst baseline fatigue, unadjusted results indicate apparent improvements in fatigue score over time for both treatments during the first 6 cycles of BR therapy, and subsequently greater continued improvements in fatigue were observed with ibrutinib + BR versus placebo + BR (p < 0.05 at cycle 10) (Figure 1). Similarly, for those with the worst baseline fatigue, mean hemoglobin values appear to increase over time after cycle 2, with comparable changes in each arm (Figure 2). In addition, of the patients who reported feeling ill or unwell at baseline (item 38 on CLL16), a greater proportion reported a return to wellness with ibrutinib + BR (40.0%) versus placebo + BR (27.3%) at cycle 10. This pattern was consistently observed from cycle 2 through cycle 19. Conclusions: These data suggest that addition of ibrutinib to BR is not associated with a negative impact on HRQL and that, among patients with the worst fatigue at baseline, ibrutinib appears to be associated with greater reductions in fatigue versus placebo. Improvements in fatigue appear to be consistent with improvements in hemoglobin and improvements in CLL disease status. Disclosures Traina: Janssen: Employment. Fraser:Hoffman LaRoche: Consultancy, Honoraria; Janssen: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding. Cramer:Astellas: Other: Travel grant; Mundipharma: Other: Travel grant; Glaxo Smith Klein/Novartis: Research Funding; Janssen: Other: Travel grant, Research Funding, Speakers Bureau; Hoffman LaRoche: Other: Travel grant, Research Funding, Speakers Bureau; Gilead: Other: Travel grant, Research Funding. Santucci Silva:Novartis: Other: Travel reimbursement; Merck: Research Funding; Celgene: Research Funding; GSK: Research Funding; Janssen: Other: Travel reimbursement, Research Funding; Hoffman LaRoche: Other: Travel reimbursement, Research Funding. Dilhuydy:Roche: Honoraria, Other: Travel reimbursement; Janssen: Honoraria, Other: Travel reimbursement; Mundipharma: Honoraria. Mahler:Janssen: Employment, Other: Travel reimbursement. Salman:Janssen/J&J: Employment, Equity Ownership. Howes:Janssen/J&J: Employment, Equity Ownership.
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) | 0,000 | 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 | 0,000 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».