Interim Restaging PET/CT-Guided High Dose Sequential Induction Therapy with Autologous Stem Cell Transplantation (ASCT) Does Not Improve Outcome for Poor Prognosis Diffuse Large B-Cell Lymphoma (DLBCL). ClinicalTrials.Gov Identifier: NCT00530179
Notice bibliographique
Résumé
Abstract Abstract 500 Purpose: Approximately 55% of patients (pts) with stage 3–4 DLBCL and elevated serum LDH achieve long-term progression-free survival (PFS) following R-CHOP chemotherapy. A prospective, multicentre, phase II clinical trial was designed to evaluate the use of high dose sequential therapy with RDICEP (Rituximab, Dose-Intensive Cyclophosphamide, Etoposide, Cisplatin) then RBEAM/ASCT (Rituximab, BCNU, Etoposide, Ara-C, Melphalan) for such pts who have unfavorable interim restaging FDG-PET/CT scans after 2 cycles of RCHOP. The trial was designed to minimize false positive interim restaging PET scans by only enrolling poor prognosis pts, and modifying response interpretation criteria such that unfavorable PET response required more than 1 site with uptake more intense than background liver. The use of RDICEP-RBEAM/ASCT built on our prior encouraging experience with DICEP-BEAM/ASCT for poor prognosis aggressive lymphoma (Blood 2006; 107: 4623–4627). The hypothesis was that interim PET response would stratify pts into good RCHOP responders who should avoid upfront ASCT, and poor RCHOP responders who may benefit from upfront ASCT, resulting in an overall PFS rate of 80%. Patients and Methods: Pts were eligible if they were HIV negative, 18–65 years of age, with stage 3–4 DLBCL and elevated serum LDH. An FDG-PET/CT scan was performed 10–15 days following the second cycle of R-CHOP. Pts with favorable interim PET response completed 4 further cycles of RCHOP, whereas pts with unfavorable PET response received one cycle of RDICEP (Rituximab 375mg/m2 day 1 and 8, C 1.75g/m2 d2-4, E 350mg/m2 d2-4 P 35mg/m2 d2-4, G-CSF d15-21 and autologous blood stem cell collection by apheresis d21or 22) followed by one cycle of RBEAM/ASCT (R 375mg/m2 day −6 and +14, B 300mg/m2 d-6, E 200mg/m2 d-5to-2, A 400mg/m2 d-5to-2, M 140mg/m2 d-1). Both groups could receive intrathecal (IT) chemotherapy or involved field radiation (IFRT) to a single site of disease at physician discretion. The sample size of 70–80pts assumed at least 33pts would be assigned to each of the favorable and unfavorable PET response groups, providing a lower limit of 66% for the 95% confidence interval around the expected 80% PFS rate. Results: Target accrual of 70 pts was achieved 5/2007–7/2011, and 67 pts have thus far undergone interim PET/CT restaging following 2 cycles RCHOP (favorable PET=32, unfavorable PET=35). The median IPI score was 3 (IPI 3–5=60pts) and median age was 54 years (range19–65) with 15 pts (21%) older than 60 years. Although there were no statistically significant differences in pt characteristics between PET response groups, the unfavorable PET response pts numerically had more ECOG 2–4 (51% vs 44%), stage IV (86% vs 69%), >1 extranodal site (60% vs 41%), bulk>10cm (54% vs 34%), B symptoms (63% vs 41%), involved marrow (40% vs 28%). IFRT was used for 8 and 5 pts, and IT chemo used for 0 and 3 pts in unfavorable and favorable PET response groups, respectively. At a median follow-up of 24mo, the 2 year OS and PFS rates for all 67 pts are 71% (95%CI 56%, 82%), and 60% (95%CI 46%, 72%), respectively (see figure). The PFS rates for the 35 unfavorable and 32 favorable PET pts were 66% (95%CI 46, 79) and 53% (95%CI 32, 71), respectively (logrank p=0.57). Of the 35 unfavorable PET pts, 3 refused assigned ASCT, 9 (25.7%) relapsed (1 in brain), and 3 (8.6%) experienced non-relapse mortality (NRM) (day+5 post-ASCT from sepsis, 12months post-ASCT from pneumonia, and 30months post-ASCT from recurrent pneumonia and heart failure). Of the 32 favorable PET pts, 12 (37.5%) relapsed (3 in brain); 9 relapses occurred in pts with completely negative PET scans, with no uptake above blood pool. Conclusions: 1) Favorable Interim PET/CT response as defined in this study does not identify good prognosis DLBCL following RCHOPx2, 2) RDICEP-RBEAM/ASCT may decrease relapse for poor prognosis DLBCL pts with unfavorable PET response, but is associated with risks of early and delayed NRM from infection, 3) a phase III trial evaluating this PET-guided RDICEP-RBEAM/ASCT approach compared to standard RCHOP alone is probably not warranted. Disclosures: Stewart: Hoffmann La Roche: Honoraria, Research Funding. Off Label Use: Rituximab with High Dose Chemotherapy and Autologous Stem Cell Transplantation for DLBCL. Bence-Bruckler:Hoffmann La Roche: Honoraria, 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 | 0,001 | 0,001 |
| 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 | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,001 |
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 ».