Rate of Transformation and Secondary Malignancies in Follicular Lymphoma Patients Treated with First-Line Bendamustine Rituximab and Rituximab Maintenance
Notice bibliographique
Résumé
INTRODUCTION: Bendamustine-rituximab (BR) has exhibited improved outcomes in first-line therapy for Follicular Lymphoma (FL). Nevertheless, concerns regarding secondary malignancies and the transformation into aggressive lymphoma have arisen. Therefore, we aim to assess the outcomes in long-term follow-up of a cohort of FL patients treated within a tertiary care cancer centre. METHODS: Using the prospectively populated Lymphoma Data Base at the Princess Margaret Cancer Centre, we evaluated the outcomes of FL patients intended to be treated with 6 cycles of BR and 2 years of rituximab maintenance as frontline therapy between 2013 and 2022. RESULTS:137 patients were identified: at diagnosis, median age was 60 years (range 31-86), 61% had stage IV disease, 49% had elevated LDH, and 56% had high FLIPI; 126 (92%) completed 6 cycles of BR treatment, and 115 (84%) commenced rituximab maintenance (RM). At a median follow-up of 6.3 years (IQR 4.0-8.6), 5-year Progression-Free Survival (PFS), Duration of Response (DOR), and Overall Survival (OS) were 65% (95% CI, 60%–74%),72% (64–81%), and 85% (79%–92%), respectively. Disease progression occurred in 44 patients (32%), with 25 (18%) progressing within 24 months (POD24). A biopsy was performed at first progression in 42 patients (95%): 26 (62%), showed transformation to diffuse large B-cell lymphoma (DLBCL, 20/42 [48%]) or, high-grade B-cell lymphoma with CMYC +BCL2 rearrangements (6/42, 14%). Among the POD24 patients, transformation was seen in 22/25 (88%). POD24 and elevated LDH at relapse were significant predictors of transformation in univariate analysis (OR 188.4 [95% CI 35.46, -], p < .001 and OR 9.58 [95% CI 2.3-51.64], p=0.004). In multivariate analysis, for transformation risk, elevated LDH at relapse was the only factor that remained significant (OR 7.64 [95% CI,1.58,36.78], p=0.11). The median time to transformation was 10 months (IQR 5-30), and the 5-year cumulative risk of transformation was 18% [95% CI: 12.1,25.4%]. Fourteen patients (10%) underwent ASCT: in 11 (79%), the indication was tFL (10 patients as a consolidation after second-line treatment, one as third line), and in 3, relapse of FL. Furthermore, 7 (5%) patients underwent CART therapy as third line of treatment or afterward, 6 (86%) with a tFL , and one (14%) for FL. The 12-month OS after ASCT was 69.2% [95% CI: 48.2, 99.5%], and after CART was 57.1% [95% CI: 30.1, 100%]. Excluding transformation and nonmelanoma skin cancer, 17 (12.4%) patients experienced a secondary malignancy during the follow-up. Given the bias of malignancies that may be present at diagnosis, we excluded the malignancies diagnosed within the 6 months from the BR, the second malignancies were found in 14 patients (10.2%). The 5-year cumulative risk of secondary malignancies among patients was 9% [95% CI: 4.14,14%]. The median time from BR to second malignancy was 23 months (IQR 7.5-74.5). The incidence rate of secondary malignancies among patients was 22.3 per 1,000 person-year. CONCLUSION: These single-centre data are consistent with prospective clinical trial results in FL, with BR followed by RM offering prolonged 5-year PFS. However, we observed a notably higher rate of transformation to aggressive lymphomas compared to clinical trials, where rates of biopsy at progression are much lower. This observation underscores the need for biopsies at early progression/relapse, and has implications for trials designed to address markers of poor outcome (positive end of treatment PET scan or MRD), as tFL rates are underestimated when biopsies are not mandated by trial protocols. The elevated risk of secondary malignancies warrants further investigation through population-based studies.
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 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».