S201: FINAL 7-YEAR FOLLOW UP AND RETREATMENT SUBSTUDY ANALYSIS OF MURANO: VENETOCLAX-RITUXIMAB (VENR)-TREATED PATIENTS WITH RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA (R/R CLL)
Notice bibliographique
Résumé
Background: The Phase 3 MURANO trial (NCT02005471) reported superior progression-free survival (PFS) and overall survival (OS) with fixed-duration VenR vs bendamustine (B)R in patients (pts) with R/R CLL. At the 5-year update, the median (m)PFS was 53.6 vs 17.0 months (P<0.0001), and 5-year OS rates were 82.1% vs 62.2% (P<0.0001) in pts treated with VenR vs BR, respectively (Seymour et al. Blood 2022). Aims: We report the final analyses of MURANO, with 7 years median follow-up (FU): specifically, updated PFS and OS, with minimal residual disease (MRD) evaluation, in pts treated in the main study, as well as in VenR-retreated pts in the substudy. Methods: Pts with R/R CLL were randomized to VenR (Ven 400mg daily for 2 years + monthly R for the first 6 months) or BR (6 months). In the substudy (2018 onwards), pts with progressive disease (PD) received VenR (same schedule as main study) as either re-treatment or as crossover from BR. PFS data are by investigator assessment. Peripheral blood MRD was measured centrally by allele-specific oligonucleotide-PCR and/or flow cytometry, with a <10–4 threshold for undetectable (u)MRD. Results: Baseline characteristics are presented in the Table. At final data cutoff (3 August 2022), VenR-treated pts (n=194) had a mPFS (95% confidence interval [CI]) of 54.7 months (52.3, 59.9) vs 17.0 months (15.5, 21.7) for BR-treated pts (n=195; hazard ratio [HR] 0.25). Seven-year PFS rates (95% CI) were 23.0% (16.1, 29.9) with VenR, while no pts treated with BR remained progression-free at this time point; 7-year OS rates (95% CI) were 69.6% (62.8, 76.5) with VenR and 51.0% (43.3, 58.7) with BR (HR 0.53). Median time to next treatment with VenR was 63.0 months vs 24.0 months with BR (HR 0.30); 37.1% of VenR-treated pts have not received subsequent anti-CLL treatment. Among VenR-treated pts who had uMRD at end of treatment (EOT) without PD (n=83/118; 70.3%), mPFS (95% CI) from EOT was 52.5 months (44.5, 61.5) vs 18.0 months (8.5, 29.3; p<0.0001) in pts who were MRD+ at EOT (n=35; 29.7%). Fourteen (16.9%) pts had no PD nor confirmed MRD conversion at the 7-year update; in the 63 (75.9%) pts who had MRD conversion, median time to conversion (95% CI) was 19.4 months (8.7, 28.0). Among 63 pts who converted, 39 subsequently had PD or died; median time from conversion to PD (95% CI) was 28.3 months (23.2, 35.0). In the substudy (n=34), 25 pts received VenR re-treatment (Table), 92.0% of whom had at least one of the following high-risk features: IGHV-unmutated disease, genomic complexity, or del(17p) and/or TP53 mutations (Wu et al. EHA 2021); despite this, 14/25 (56.0%) achieved uMRD at EOT in the main study. Best overall response rate (ORR) to re-treatment was 72.0% and mPFS (95% CI) was 23.3 months (15.6, 24.3). Median (range) time between the last Ven dose in the main study and Ven ramp-up in the substudy was 2.3 (1.2–3.1) years. Eight (32.0%) pts achieved uMRD at the re-treatment end of combination treatment; however, no pts retained their uMRD status at the re-treatment EOT. No new safety findings were observed since the 5-year data cut. Summary/Conclusion: In this final long-term analysis of the MURANO trial, PFS and OS benefits for VenR over BR were sustained. Furthermore, achievement of uMRD was associated with prolonged PFS. In VenR-treated pts in the substudy, ORR was high and uMRD was still attainable in this high-risk population. Overall, these data continue to support the use of fixed-duration VenR in R/R CLL, and suggest that re-treatment with VenR is a viable option for pre-treated pts.Keywords: Retreatment, Chronic lymphocytic leukemia, Minimal residual disease (MRD), Venetoclax
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 | 0,003 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,000 | 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) | 0,002 | 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 ».