Significance of Prior HSCT on the Outcome of Salvage Therapy with CPX-351 or Conventional Chemotherapy Among First Relapse AML Patients
Notice bibliographique
Résumé
Abstract Abstract 2619 Background: CPX-351 is a liposomal formulation containing a 5:1 molar ratio of cytarabine (Ara-C) and daunorubicin (DNR) designed to maximize anti-tumor synergy (Mayer L, et al. Mol Can Ther, 2006;5:1854). In the Phase 1 study 18/45 AML patients were in 1st relapse with 8 patients ≤65 years of age. All 8 achieved aplasia and 4/8 achieved CR after CPX-351 treatment. (Feldman E, et al. Blood 2008;112:Abst 2984). These observations provided the rationale for a randomized Phase 2b study in 1st relapse AML patients comparing CPX-351 against investigator's choice of salvage regimen. An initial safety and efficacy summary has been submitted to this meeting. This report summarizes the impact of prior HSCT on patient response and 60 day mortality. Methods: Patients ≤65yo with AML in 1st relapse after an initial CR lasting >1 month with ECOG PS= 0–2, SCr <2.0 mg/dL, total bilirubin <2.0 mg/dL, ALT/AST <3 × ULN, and LVEF ≥50% were eligible. Patients were randomized 2:1 to receive CPX-351 (100 u/m2; D 1, 3, 5) or investigators choice of intensive salvage treatment. Up to 2 induction and 2 consolidation courses were allowed. Post remission treatment with HSCT was permitted. Patients were stratified using the European Prognostic Index (EPI) (Breems DA, et al. J Clin Oncol, 2005 Mar 20;23:1969–1978). The primary efficacy endpoint is % survival at 1 year. Results: By November 12, 2010, 126 patients were accrued at 35/46 sites in the US, Canada, France, Poland. Data for response, acute safety, and 60 day deaths are available. Patients in both arms were well balanced by Relapse Free Interval (RFI), age at 1st relapse and cytogenetics. More patients with prior HSCT were assigned to the CPX-351 arm (27% v. 18%). Table 1 shows patient characteristics organized by presence or absence of prior HSCT. Among patients with prior HSCT, the CPX-351 arm had more patients with RFI ≤6 months (36% v. 0%) and younger patients (age <45, 36% v. 13%). The group with no prior HSCT was balanced for overall risk by EPI, RFI, age at 1st relapse, and adverse cytogenetics. For the overall study, the CPX-351 arm had higher aplasia (90% v. 60%) and CR + CRi rate (51% v. 42%) and similar 60 day mortality (15% v. 16%) compared to control. Table 2 shows patient response and early mortality organized by presence or absence of prior HSCT. In the 96 patients (76%) with no prior HSCT, CPX-351 produced an increased rate of aplasia compared to control (90% v. 57%), a response rate that was greater than control (56% v. 41%), and a lower 60 day mortality rate (10% v. 16%). HSCT had little observed impact on outcomes in the control arm but appears to be associated with reduced aplasia (90% to 55%) and response (56% to 36%) and a disproportionate contribution to early deaths (6/12) in the CPX-351 arm. The higher proportion of patients with RFI ≤6 months on the CPX-351 arm (36% v. 0%) may be a contributing factor. Conclusion: Eighty six/126 (68%) patients had unfavorable risk by EPI with equal proportions randomized to each arm of the study. Prior HSCT had little impact on outcomes in the control arm but seemed to have a much larger adverse impact on the CPX-351 arm. This observation of a change in outcome associated with prior HSCT may be due to the higher proportion of patients with RFI ≤6 months on the CPX-351 arm (36% v. 0) and is being evaluated further. Additional data (EFS, % survival at 1 year) are expected later this year. Disclosures: Cortes: Celator: Membership on an entity's Board of Directors or advisory committees. Louie:Celator: Employment.
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 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| 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 | 0,001 | 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 ».