3-year follow-up of the S1826 study confirms improved progression-free survival with nivolumab-AVD compared to brentuximab vedotin-AVD in advanced stage classic Hodgkin lymphoma
Notice bibliographique
Résumé
Abstract Introduction: The randomized phase 3 S1826 study demonstrated that, in adolescent and adult patients (pts) with previously untreated advanced stage (AS) classic Hodgkin lymphoma (cHL), PD-1 blockade with nivolumab in combination with doxorubicin, vinblastine, and dacarbazine (N-AVD) prolonged progression-free survival (PFS) compared with standard brentuximab vedotin (BV) combined with AVD at a median follow-up of 2 years. The PFS benefit was consistent across patient subgroups, N-AVD was better tolerated than BV-AVD, and radiation (RT) was rarely utilized. Herein, we evaluate durability of these results with a median follow-up of 3 years (y). Methods: Eligible pts were ≥12y with stage 3-4 cHL. Pts were randomized in a 1:1 ratio to receive either 6 cycles of N-AVD or BV-AVD. Pts were stratified by age, international prognostic score (IPS), and intent to use RT. G-CSF prophylaxis was mandatory with BV-AVD; it was optional with N-AVD. RT (30 Gy) to residually metabolically active lesions at the end of treatment was allowed according to pre-specified criteria. Pathology was centrally reviewed, patients without confirmation of cHL were ineligible for modified intent-to-treat (mITT) analysis. Response and disease progression were assessed by investigators using 2014 Lugano Classification. The primary endpoint was PFS; secondary endpoints included safety, event-free survival (EFS), patient-reported outcomes, and overall survival (OS). The database was locked for analysis on July 1, 2025. Results: 994 pts were enrolled from 7/9/19 to 10/5/22 and randomized to N-AVD (n=496) or BV-AVD (n=498). 970 (98%) were eligible and comprised the mITT cohort. Median age was 27y (range, 12-83y), 56% of pts were male, 76% were white, 12% were black, and 13% were Hispanic. 24% of pts were < 18y, 10% were > 60y, and 32% had IPS 4-7. Only 7 (0.7%) pts across arms received RT. With 3.1y of median follow-up (range, 0-5.5y), the PFS advantage with N-AVD was sustained (HR 0.48, 95%CI 0.34-0.69, one-sided p<0.0001), with 3y PFS of 91% after N-AVD compared to 82% after BV-AVD. As previously, the PFS benefit was significant across all age, stage, and IPS subgroups. Among pts ages 18-60y, 3y PFS in pts who received N-AVD was 91% compared to 85% in pts treated with BV-AVD (HR 0.61, 95% CI 0.38-0.96). Among adolescent pts ages 12-17y, 3y PFS in pts who received N-AVD was 93% vs 82% after BV-AVD (HR 0.36, 95% CI 0.17-0.79). In pts older than 60y, 3y PFS was 82% after N-AVD vs 58% after BV-AVD (HR 0.33, 95% CI 0.14 – 0.77). Pts with Stage IV cHL who received N-AVD had 3y PFS 89% compared to 80% after BV-AVD (HR 0.55, 95% CI 0.36-0.83), and had similar PFS to pts with stage III cHL who received N-AVD (3y PFS 93% vs 86% with BV-AVD, HR 0.42, 95% CI 0.22-0.81). Likewise, N-AVD led to improved PFS among pts with IPS scores of 4-7 (3y PFS 87% vs 77% with BV-AVD, HR 0.57, 95% CI 0.33-0.97). Pts with IPS 0-3 had longer PFS with N-AVD (3y PFS 92%) than with BV-AVD (3y PFS 84%, HR 0.45, 95% CI 0.28-0.72). EFS was also improved after N-AVD (HR 0.56, 95% CI 0.41-0.78, p=0.0004). There were 15 deaths observed after BV-AVD (3y OS 97%) compared to 8 after N-AVD (3y OS 98%, HR 0.48, 95% CI 0.20-1.15, p=0.092). No new safety signals were observed. Second cancers were observed in 6 (1.2%) pts after N-AVD (4 non-Hodgkin lymphomas [NHL], 1 skin cancer, 1 solid tumor) vs 11 (2.3%) pts after BV-AVD (3 NHL, 1 multiple myeloma, 7 solid tumors). Conclusions: The benefit of N-AVD compared to BV-AVD in adolescent and adult pts with AS cHL is sustained with 3y follow-up, including all pre-specified age, stage, and IPS risk subgroups. This update demonstrates the durability of remissions with N-AVD over time without any new safety signals, and enables benchmarking with other modern cHL trials. Follow-up will continue to evaluate for late toxicities, OS, and PROs. These results validate guidelines recommending N-AVD as a preferred frontline treatment regimen in patients with AS cHL, including high-risk patients.
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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 | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| 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 | 0,001 | 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 ».