Five-Year Analysis of the POLARIX Study: Prolonged Follow-up Confirms Positive Impact of Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (Pola-R-CHP) on Outcomes
Notice bibliographique
Résumé
Background: In thePOLARIX study (NCT03274492), Pola-R-CHP showed a significant progression-free survival (PFS) benefit vs R-CHOP in patients (pts) with intermediate- or high-risk DLBCL at a median follow-up of 28 months (Tilly et al. NEJM 2022). Here, we report outcomes after 5 years of follow-up (cut-off, 5 July 2024). Methods: POLARIX methods were published in Tilly et al. NEJM 2022. Pts 18-80 years were randomized 1:1 to receive 6 cycles of Pola-R-CHP or R-CHOP, plus 2 cycles of rituximab. The primary endpoint was PFS. In this analysis, 1000 pts (expanded population) were evaluated; 879 pts (global ITT population) from the main study (enrolled Nov 2017-Jun 2019) and 121 pts from a Chinese extension cohort (enrolled Jul 2019-Dec 2020; Song et al. Blood 2023). Extended follow-up of efficacy and safety are described. A competing risk analysis assessed the risk of death from lymphoma vs other causes. Results: In the global ITT population, 879 (Pola-R-CHP, n=440; R-CHOP, n=439) and 873 pts (Pola-R-CHP, n=435; R-CHOP, n=438) were evaluable for efficacy and safety, respectively. In the expanded population, 1000 (Pola-R-CHP, n=500; R-CHOP, n=500) and 993 pts (Pola-R-CHP, n=495; R-CHOP, n=498) were evaluable for efficacy and safety, respectively. In the global ITT population (median follow-up 60.9 months), the 5-year PFS estimates were 64.2% (95% CI: 58.78-69.53) vs 59.1% (95% CI: 53.87-64.40) with Pola-R-CHP vs R-CHOP, showing a significant benefit (HR 0.78; 95% CI: 0.623-0.980). The 5-year OS estimates were 82.2% (95% CI: 78.53-85.82) vs 79.6% (95% CI: 75.70-83.47) with Pola-R-CHP vs R-CHOP, with an improved HR (0.87; 95% CI: 0.641-1.175) compared with the 2-year follow-up HR (0.94; 95% CI: 0.650-1.370). The 5-year disease-free survival (DFS) estimates were 71.3% (95% CI: 65.46-77.05) vs 65.5% (95% CI: 59.45-71.45) with Pola-R-CHP vs R-CHOP (HR 0.75; 95% CI: 0.570-0.992). In the expanded population (median follow-up 60.5 months), a similar significant 5-year PFS benefit was observed, with estimates of 63.1% (95% CI: 57.90-68.26) vs 59.1% (95% CI: 54.07-64.15) with Pola-R-CHP vs R-CHOP (HR 0.81; 95% CI: 0.652-0.996). The number of pts requiring subsequent systemic lymphoma therapy was 106 (21%) vs 145 (29%) with Pola-R-CHP vs R-CHOP. The 5-year OS estimates were 82.2% (95% CI: 78.78-85.68) vs 79.0% (95% CI: 75.24-82.70) with Pola-R-CHP vs R-CHOP, with no statistically significant difference (HR 0.84; 95% CI: 0.632-1.119). The 5-year DFS estimates were 69.4% (95% CI: 63.78-75.05) vs 65.1% (95% CI: 59.30-70.92) with Pola-R-CHP vs R-CHOP (HR 0.81; 95% CI: 0.625-1.042). Safety profiles were comparable with Pola-R-CHP vs R-CHOP across all safety-evaluable pts in the expanded population (n=993), including Grade 3-5 AE rates (62.6% vs 60.8%). Fewer secondary malignancies were observed with Pola-R-CHP (n=5) vs R-CHOP (n=12). No new safety signals were observed during long-term follow-up; similar rates of new serious AEs were reported with Pola-R-CHP and R-CHOP (1.8% and 2.2%, respectively). No new cases of peripheral neuropathy were reported. Serious infections occurred in 4 pts (0.8%) vs 1 (0.2%) pt with Pola-R-CHP vs R-CHOP. In the expanded population, fewer total deaths were observed in pts treated with Pola-R-CHP vs R-CHOP (90 vs 107). Lymphoma-related deaths occurred in 46 vs 62 pts with Pola-R-CHP vs R-CHOP (during the first 2 years, 32 vs 39 pts; beyond 2 years, 14 vs 23 pts for Pola-R-CHP vs R-CHOP). Similar numbers of deaths from infection (7 vs 11), cardiovascular disease (4 vs 5), and secondary malignancy (7 vs 5) were observed with Pola-R-CHP vs R-CHOP. In a competing risk analysis, with non-lymphoma-related deaths (including death due to study treatment) as competing events, the cumulative incidence of lymphoma-related death at 5 years was 9.1% vs 12.2% for Pola-R-CHP vs R-CHOP. Conclusions: Extended 5-year follow-up of POLARIX demonstrated sustained and significant PFS and DFS benefits for pts receiving Pola-R-CHP vs R-CHOP. OS was reassuring between pts with Pola-R-CHP and R-CHOP, with more deaths, including lymphoma-related deaths, observed with R-CHOP. With the observation that a higher proportion of pts receiving R-CHOP died beyond 2 years, prolonged follow-up will be of interest. Safety profiles remained similar between arms, and no new safety signals were identified. These outcomes confirm Pola-R-CHP as a standard of care for pts with previously untreated intermediate- or high-risk DLBCL.
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 | 0,008 | 0,005 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,003 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,002 |
| 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 ».