Rituximab Improves Overall Survival In Patients Treated With CODOX-M/IVAC For Burkitt Lymphoma (BL) and B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and BL: A Single Center Experience and Review Of The Literature
Notice bibliographique
Résumé
Abstract Background Dose-modified(dm) CODOX-M/IVAC is commonly used for Burkitt lymphoma (BL) and overlap aggressive B cell lymphomas (B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and BL, previously Burkitt-like lymphoma-BLL), with high cure rates, but significant toxicity. The concurrent use of rituximab with CODOX-M/IVAC is relatively new in both BL and BLL. Methods: We undertook this retrospective study of BL and BLL patients treated at a large quaternary care cancer center with dmCODOX-M/IVAC +/-rituximab(R) in order to a) determine ‘real-world' toxicity and survival rates, b) examine the effects of BL versus intermediate histology diagnoses, and c) evaluate the effects of rituximab (R) use. Patients diagnosed between January 2006-December 2012 as having either Burkitt lymphoma or atypical Burkitt/Burkitt-like lymphoma (WHO Classification 2001), or B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and BL (WHO 2008) and who had received the dmCODOX-M/IVAC regimen,+/- R within 2 months of their diagnosis, were identified. In May 2008, we adopted the practice of adding R 375 mg/m2 to dmCODOX-M/IVAC in non-HIV patients due to emerging data from other centers. In 2012, our approach to BLL was altered, by adding 1-4 cycles of R-CHOP after the dmCODOX-M/IVAC protocol completion, to maximize anthracycline and rituximab delivery. The primary outcomes of interest were 2-year overall (OS) and progression-free survival (PFS). Univariate and multivariable Cox proportional hazard models of OS and PFS were constructed. Results: 31 patients with BL (n=21) or BLL (n=10) were included. The median age was 45, and 90% were high risk. 94% of patients displayed a MYC translocation (t(8;14)) by FISH cytogenetics. Additionally, 8 (26%) patients were BCL2+ by immunohistochemistry (IHC). Three were also positive for the t(14;18) (double-hit lymphomas), and one was unknown. Because of the diagnostic uncertainty (pending MYC status), 10 (32%) began treatment with chemotherapy other than dmCODOX-M/IVAC (mostly 1-2 cycles of CHOP+/-R). The median time from diagnosis to first chemotherapy was 13 days (1-58) and from first chemo to first HDMTX 10.5 days (0-57). In total, 22 (71%) patients received at least one infusion of rituximab at some point during first line treatment with a median of 3 infusions (range 1-7). Five of 10 BLL patients (50%) received a median of 2 additional R-CHOP cycles (range 1-4). In the patients who received R-CHOP first vs. those who did not, the median time from diagnosis to the first chemotherapy was 9 days (range: 1-21) compared with 17 days (range: 0-58) (p=0.29). Despite GCSF use, 24 patients (77%) experienced at least one episode of febrile neutropenia post dmCODOX-M and 12 patients (39%) post dmIVAC. The 2-year overall survival (OS) and progression-free survival (PFS) were 69% and 62%, respectively, with no differences between BL and BLL (Figure 1). When BLL was separated by whether R-CHOP was given, there were still no differences in OS between BL, BLL (“no R-CHOP after”) and BLL (“R-CHOP after”) (2-yr OS 64% vs. 60% vs. 100%, p=0.38; Figure 1). Patients who received rituximab had superior OS (2-yr OS 86% vs. 33%, p=0.0013; Figure 1) compared with those that did not. Starting with CHOP-R versus dmCODOX-M was associated with an OS benefit (2-yr OS 100% vs. 53%, p=0.009; Figure 1), despite no difference in OS whether time from diagnosis to first chemotherapy was ≥ or < 10 days (p=0.96) By multivariable analysis, rituximab use was significantly associated with improved OS (HR 0.15; 95%CI 0.04-0.56) and PFS (HR 0.05; 95%CI 0.01-0.32). Conclusion The addition of rituximab to dmCODOX-M/IVAC improves overall and progression free survival in both BL and BLL and is recommended. BLL is a challenging histology to treat with inferior outcomes to DLBCL when treated similarly. The use of an aggressive regimen such as R-dmCODOX-M/IVAC in BLL can yield promising results that are comparable to BL. Disclosures: No relevant conflicts of interest to declare.
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) | 0,000 | 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 ».