Mature Results From ECOG Study E1405 – A Phase II Study of VcR-CVAD with Maintenance Rituximab for Previously Untreated Mantle Cell Lymphoma
Notice bibliographique
Résumé
Abstract Abstract 153 Introduction Modified R-hyperCVAD is a well-tolerated induction regimen with a high response rate in MCL. We hypothesized that the incorporation of bortezomib (Velcadea) into this regimen would enhance the complete response rates. We further hypothesized that the addition of maintenance rituximab (MR) would improve remission duration. The new regimen, VcR-CVAD with MR, was tested for safety and efficacy in the Eastern Cooperative Oncology Group. Methods Eligible patients had histologically confirmed, previously untreated MCL, PS 0–2, and adequate end organ function. The treatment plan included: bortezomib 1.3 mg/m2 days 1 and 4, rituximab 375 mg/m2 IV day 1, cyclophosphamide 300 mg/m2 IV over 3 hrs q 12 hrs × 6 doses days 1–3, doxorubicin 50 mg/m2 continuous infusion over 48 hrs days 1–2, vincristine 1 mg IV day 3, dexamethasone 40 mg po days 1–4. Cycles were repeated every 21 days for 6 cycles and all patients received G-CSF support. Patients achieving SD, PR, or CR received MR administered as 4 weekly treatments every 6 months for 2 years (protocol therapy). Patients could elect to receive high dose chemotherapy and autologous stem cell transplantation (SCT) off protocol rather than MR. The primary endpoint of the trial was the CR rate, defined as PET-negative, marrow-negative, to VcR-CVAD induction therapy. Results Seventy-five eligible patients were enrolled between 5/07 and 10/08. Baseline characteristics include median age 62 (40–76), 58M:17F, 92% stage III/IV, and 40% with elevated LDH. MIPI risk distribution included 37% low, 36% intermediate, 19% high, 8% unknown. Sixty-eight patients (91%) completed VcR-CVAD induction therapy. Reasons for treatment discontinuation included PD (1), toxicity (4), and patient preference (2). The ORR was 97% (73/75), CR rate 68% (51/75) and PR rate 29% (22/75). Of the 22 PR patients, 11 were so coded due to no bone marrow evaluation and/or PET imaging post therapy. The CR rate in the 64 completely restaged patients was 80%. Forty-four patients proceeded to protocol planned MR while 22 patients received SCT consolidation off protocol. With a median follow up of 3.6 years, the 3-yr PFS for the MR cohort (n = 44) and entire cohort (n = 75) are 73% and 74%, respectively. OS at 3-yrs is 88%, with no difference between MR and SCT patients. The major toxicity of the induction treatment regimen was expected myelosuppression. Grade 3–4 non-hematologic toxicities were rare. No patients developed grade 3–4 neuropathy. There were no serious toxicities during MR. There were no treatment related deaths. Conclusion The VcR-CVAD induction produced high overall OR (97%) and CR rates (68%) in a representative MCL patient population treated in a cooperative group setting. The 3-yr PFS (74%) and OS (88%) are highly encouraging. Remissions in patients receiving MR were as durable as patients receiving SCT consolidation. The value of bortezomib, when added to conventional chemotherapy, is currently being tested in a randomized intergroup trial (E1411). Disclosures: Kahl: Genentech: Consultancy, Research Funding; Roche: Consultancy; Millennium: Consultancy, Research Funding. Off Label Use: Bortezomib as frontline treatment of mantle cell lymphoma. Smith:Millennium: Research Funding. Advani:Genentech: Research Funding. Horning:Genentech: Employment; Roche: 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 | 0,009 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».