CPX-351 Is Effective in Newly Diagnosed Older Patients with AML and with Multiple Risk Factors
Notice bibliographique
Résumé
Abstract Abstract 3626 Background: CPX-351 is a liposomal formulation of cytarabine (Ara-C) and daunorubicin (DNR) in a 5:1 molar ratio designed to maximize anti-tumor synergy. CPX-351 accumulates within bone marrow with preferential uptake of liposomes by leukemia cells followed by intracellular release of encapsulated drug. A Phase 2b study randomized untreated older patients with AML 2:1 to CPX-351 or standard 7+3. At entry patients were stratified by age, cytogenetics, and presence or absence of antecedent hematologic disorder (AHD)/prior cytotoxic treatment that evolved into AML (sAML) into a high-risk group (age ≥70 or adverse cytogenetics or sAML) or standard-risk group (age 60–69 and non-adverse cytogenetics and de novo AML). The standard-risk group was relatively homogeneous, while the high-risk group gathered together patients with one, two or all three risk factors. Response after CPX-351 was increased in all patients (66.7% vs. 51.2%). Patients with secondary AML had coherent improvement in survival (HR=0.40, p=0.01), EFS (HR=0.51, p=0.04), and CR + CRi rate (57.6% vs. 31.6%). This report presents the results of uni/multivariate analyses for survival and event free survival. Methods: Untreated de novo or sAML patients, aged 60–75, PS= 0–2, serum creatinine < 2.0 mg/dL, total bilirubin < 2.0 mg/dL, ALT/AST < 3 × ULN, and LVEF ≥50% were eligible. Patients with history of treatment for their AHD were eligible. Patients received up to 2 induction and 2 consolidation courses of CPX-351 (100 u/m2; D 1, 3, 5) or 7+3 (Ara-C= 100 mg/m2/d and DNR= 60 mg/m2). Consolidation with hematopoietic stem cell transplantation (HSCT) was permitted. The primary endpoint was CR + CRi rate. Event free survival was calculated from randomization to the date of documentation of persistent leukemia after induction, relapse after achievement of response, or death, whichever occurred first. Allogeneic transplants were permitted for post remission treatment. The association between baseline characteristics and survival was assessed by univariate and multivariate Cox regression analyses. Response was included as a time-dependent variable. The multivariate model used stepwise selection to identify prognostic factors after accounting for potential treatment effects. Results: Significant factors affecting overall survival (OS) in the univariate analysis included: response (p=0.01), ≥2 risk factors (p=0.013), secondary AML (p=0.021), and adverse cytogenetics (p=0.038). After accounting for treatment, response (p=0.003) and ≥2 risk factors (p=0.005) were strongly associated with OS in the multivariate model. Response and 60-day deaths were similar in both study arms for patients with 0 or 1 risk factor. Patients with 2 or 3 risk factors treated with CPX-351 had rates of response and 60-day death rates that were similar to those with only 0 or 1 risk factor. Control arm patients with multiple risk factors did much worse, with fewer CRs, no CRi's, and a substantially higher rate of early deaths. Conclusions: CPX-351 is highly active in every subgroup of older patients with newly diagnosed AML. This analysis demonstrates that CPX-351 minimizes the loss of response and increase in 60-day mortality that occurs with 7+3 treatment among patients with secondary AML and adverse cytogenetics. The relative benefit of CPX-351 is greatest among patients with ≥ 2 risk factors. Disclosures: Lancet: Celator Pharmaceuticals: Research Funding. Cortes:Celator Pharmaceuticals: Research Funding. Kovacsovics:Celator Pharmaceuticals: Research Funding. Hogge:Celator Pharmaceuticals: Research Funding. Kolitz:Celator Pharmaceuticals: Research Funding. Hoering:Celator Pharmaceuticals: Consultancy. Chiarella:Celator Pharmaceuticals: Employment. Louie:Celator Pharmaceuticals: Employment. Feldman:Celator Pharmaceuticals: Research Funding.
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 | 0,000 | 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 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».