PF294 IMPROVED OUTCOMES IN PATIENTS (PTS) WITH BCL2‐POSITIVE DIFFUSE LARGE B‐CELL LYMPHOMA (DLBCL) TREATED WITH VENETOCLAX (VEN) PLUS R‐CHOP: RESULTS FROM THE PHASE 2 CAVALLI STUDY
Notice bibliographique
Résumé
Background: BCL2 overexpression, concurrent overexpression of BCL2 and MYC, and coexisting translocations of BCL2 and MYC (double‐hit [DH]) are associated with poor outcome in DLBCL. Ven, a highly selective BCL2 inhibitor, may enhance the current standard regimen of rituximab (R) plus CHOP chemotherapy. The phase (Ph) 1b part of CAVALLI (NCT02055820) established Ven 800 mg, given Days (D) 1−4, Cycle (C) 1 and D1−10, C2−8, as the recommended Ph 2 dose in combination with R‐CHOP in first‐line (1L) DLBCL. Aims: We report safety, efficacy, and biomarker analyses of the Ph 2 part of CAVALLI (data cut‐off, July 13, 2018). Methods: Eligible pts were aged ≥18 years with 1L DLBCL, ECOG performance status ≤2 and International Prognostic Index (IPI) score 2–5. Ven 800 mg was given orally on D1–4, C1 and D1−10, C2−8 combined with R (8 Cs) and CHOP (6−8 Cs); 21‐day Cs. The primary endpoint was positron emission tomography (PET)‐complete response (CR) rate at end‐of‐treatment (EOT; modified Lugano criteria 2014). Secondary endpoints were progression‐free survival (PFS), overall survival (OS), and safety. The R‐CHOP control arm of GOYA (564 pts with IPI 2–5) was selected as a historical control. Factors affecting completion of 8 treatment Cs were assessed using multivariate analysis (MVA). Time‐to‐event endpoints were compared using adjusted Cox regression. Biomarker analyses included BCL2 and MYC expression by immunohistochemistry (IHC; cut‐off, 50% medium/high expression [BCL2] and >40% any expression [MYC]), BCL2 and MYC translocations by fluorescence in situ hybridisation (FISH), and cell‐of‐origin (COO) by NanoString. Results: Overall, 211 pts were enrolled in CAVALLI; 208 received any treatment and were analyzed for efficacy and safety. Baseline characteristics for CAVALLI vs GOYA were similar, but more Ann Arbor Stage IV (65% vs 47%) and BCL2 IHC+ (58% vs 49%) pts were enrolled in CAVALLI. In the overall population, PET‐CR rates at EOT were comparable (CAVALLI, 69%; GOYA, 63%); however, PET‐CR rates were higher in CAVALLI for BCL2 FISH+ and DH pts ( Table ). PFS was improved in the overall and BCL2 IHC+ populations vs GOYA ( Figure ). The PFS benefit in the BCL2 IHC+ population was observed across both ABC and GCB COO subtypes. Evidence of OS improvement vs GOYA was also seen; HR 0.7, 95% CI 0.43–1.1 (overall), HR 0.7, 95% CI 0.35–1.2 (BCL2 IHC+). Grade 3–4 adverse events (AEs) occurred in 86% (179/208) of pts in CAVALLI vs 66% (373/564) in GOYA, mainly cytopenia, febrile neutropenia (FN), and infection. There was a trend towards lower neutropenia and FN/infection incidence in pts receiving granulocyte‐colony stimulating factor prophylaxis. On MVA, age <60 yrs was the only factor to predict completion of 8 treatment Cs (p = 0.002). There were 4 fatal AEs (2%) in CAVALLI vs 30 (5%) in GOYA, but follow‐up was longer in GOYA (29.6 vs 22.3 months). The high rate of AEs in CAVALLI led to Ven and R‐CHOP dose interruptions/discontinuations; 61% of pts received >90% relative dose intensity (RDI) of Ven; 73% received >90% RDI for cyclophosphamide and doxorubicin. The RDI of chemotherapy was similar in GOYA. Summary/Conclusion: Addition of Ven to R‐CHOP in 1L DLBCL resulted in improved efficacy in BCL2 IHC+ pts compared with matched GOYA controls. A higher rate of cytopenia, FN and infections was observed in CAVALLI vs GOYA; however, there was no increase in risk of death, and the RDI of chemotherapy was maintained at similar levels. image
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| 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) | 0,001 | 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 tête enseignante, 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 ».