Age Subgroup Analysis of Health-Related Quality of Life of Blinatumomab Versus Standard-of-Care Chemotherapy in Patients with Relapsed or Refractory Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia in a Randomized, Open-Label, Phase 3 Study (TOWER)
Notice bibliographique
Résumé
Abstract Background: Despite the availability of new therapies for acute lymphoblastic leukemia (ALL), older patients have historically poor responses to treatment and poor outcomes versus younger patients, with 5-year survival rates of approximately 20% or less. Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that redirects cytotoxic T cells to lyse CD19-positive B cells and is approved for the treatment of relapsed or refractory (r/r) B-cell precursor (BCP) ALL and for minimal residual disease-positive ALL in the US. In the phase 3 TOWER study in patients with r/r Philadelphia chromosome-negative (Ph-) BCP ALL who received blinatumomab compared with standard-of-care (SOC) chemotherapy, overall survival was improved (median, 7.7 vs 4.0 months; P=0.01; Kantarjian H, et al. N Engl J Med. 2017;376:836-847), and posttreatment health-related quality of life (HRQoL) across all EORTC QLQ-C30 scales was better (Topp MS, et al. Blood. 2018;131:2906-2914). TOWER efficacy results did not differ by age group. In this subgroup analysis of TOWER, we assessed the HRQoL of older patients versus younger patients who received blinatumomab or SOC chemotherapy. Methods: Patients (N=405) with r/r Ph- BCP ALL were randomized 2:1 to receive 2 cycles of induction blinatumomab by continuous intravenous infusion (n=271) or SOC (n=134). Patients could receive transplant at any time following cycle 1. Those in remission could receive up to 3 consolidation cycles; 12 months of maintenance was allowed for those who received up to 3 consolidation cycles and had bone marrow response. HRQoL was assessed using the EORTC QLQ-C30 Questionnaire on days 1 (baseline), 8, and 15, on day 29 of cycle 1; day 1, 15, and 29 of each consolidation cycle; and at the safety follow-up. The questionnaire included 1 global health status scale, 5 functioning scales, 3 symptom scales, and 6 single-symptom items. For global health status and functioning scales, a higher score indicates better HRQoL; for symptom scales/items, a lower score indicates better HRQoL. A 10-point change was viewed as the minimum clinically important difference in EORTC QLQ-C30 (Zikos E, et al. EORTC. 2016). In this analysis, HRQoL in TOWER was assessed using two different age cutoffs: <35 versus ≥35 years (the randomization stratification in TOWER) and <55 versus ≥55 years (the stratification factor for INO-VATE, a phase 3 trial for another therapy in r/r ALL). Analyses included patients with baseline and ≥1 postbaseline result of any multi-item scale or single-item measure. Mean change from baseline in scores for each scale/item were summarized for cycle 1. Time to deterioration (TTD) analyses assessed the treatment effect based on timing from the initiation of treatment to a ≥10-point decrease for the functional scales and/or a ≥10-point increase for the symptom scales respectively. Conclusions: Consistent with the efficacy results, compared with SOC, blinatumomab improved HRQoL and delayed the deterioration in HRQoL regardless of the age group in patients with r/r Ph- BCP ALL. Disclosures Topp: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Boehringer Ingelheim: Research Funding; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron Pharmaceuticals, Inc.: Honoraria, Research Funding. Zimmerman:Amgen Inc.: Employment, Equity Ownership. Dombret:Cellectis: Consultancy, Honoraria, Other: Travel expenses; Servier: Consultancy, Honoraria; Immunogen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Ambit (Daiichi Sankyo): Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Menarini: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Shire-Baxalta: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Otsuka: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Kite Pharma: Consultancy, Honoraria, Research Funding; Jazz Pharma: Consultancy, Honoraria, Research Funding; Ariad (Incyte): Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau; Roche/Genentech: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau. Stein:Celgene: Speakers Bureau; Amgen Inc.: Speakers Bureau. Franklin:Amgen Inc.: Employment, Equity Ownership. Cong:Amgen, Inc.: Employment, Equity Ownership. Zhang:Amgen Inc.: Employment, Equity Ownership. Schuh:Amgen Inc.: Consultancy; Pfizer: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Otsuka: Consultancy; Shire: Consultancy; Teva: Consultancy; Jazz: Consultancy.
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 | 0,002 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,004 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| 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 ».