LB2307. Safety and Efficacy of Letermovir (LET) versus Valganciclovir (VGCV) for Prevention of Cytomegalovirus (CMV) Disease in Kidney Transplant Recipients (KTRs): A Phase 3 Randomized Study
Notice bibliographique
Résumé
Abstract Background VGCV is approved for prophylaxis in adult KTRs at high risk for CMV disease (donor CMV-seropositive/recipient CMV-seronegative [D+/R-]); however, its use is limited by myelosuppression. LET is non-myelotoxic, does not require dose modification in renal impairment, and is approved for prophylaxis of CMV infection and disease in adult CMV-seropositive allogeneic hematopoietic stem cell transplant recipients. This randomized, double-blind, Phase 3 non-inferiority study (NCT03443869; MK-8228-002) evaluated CMV prophylaxis with LET vs. VGCV in adult CMV D+/R- KTRs. Methods Adult CMV D+/R- KTRs were randomized 1:1 within 7 days post-kidney transplant (KT) to receive either LET 480 mg QD (PO/IV) with acyclovir (400 mg PO BID, adjusted for renal function), or VGCV (900 mg PO QD, adjusted for renal function), through Week 28 post-KT and followed up through Week 52 post-KT. Randomization was stratified by use of lymphocyte-depleting induction immunosuppression. The primary endpoint was the proportion of participants (pts) with CMV disease adjudicated by blinded committee through Week 52 post-KT (non-inferiority margin,10%). Results A total of 601 pts were randomized; 589 received ≥ 1 dose of study medication (median age [range], 51 [18–82] years; male, 72%; Black/African American, 9%; deceased donor, 60%; received lymphocyte-depleting induction immunosuppression, 46%), of whom two had detectable CMV viral DNA on Day 1 and one was CMV R+ (full analysis set, 586 pts). The proportion of pts with CMV disease through Week 52 post-KT was 10.4% with LET vs. 11.8% with VGCV (stratum-adjusted treatment difference, -1.4% [95% CI -6.5, 3.8]; Table 1). Drug-related adverse events (AEs) were reported in 19.9% of pts with LET and 35.0% of pts with VGCV through Week 28 post-KT. The rate of discontinuations due to an AE was 4.1% in the LET arm and 13.5% in the VGCV arm (Table 2). The incidence of neutropenia (absolute neutrophil count < 1000/µL) during the treatment phase was lower with LET than with VGCV (4.1% vs. 19.5%; difference, -15.4% [95% CI -20.7, -10.5]). Conclusion The study met its primary endpoint: LET was non-inferior to VGCV in preventing CMV disease in high-risk (CMV D+/R-) KTRs through Week 52 post-KT, and led to a lower rate of myelotoxicity than VGCV. Disclosures Ajit P. Limaye, MD, AiCuris: Advisor/Consultant|MedPace: Data Safety Monitoring Boards|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Novartis: Data Safety Monitoring Boards|Sana: Advisor/Consultant Klemens Budde, MD, Abbvie: Grant/Research Support|Abbvie: Honoraria|Alexion: Grant/Research Support|Alexion: Honoraria|Astellas: Grant/Research Support|Astellas: Honoraria|Bristol Myers Squibb: Grant/Research Support|Bristol Myers Squibb: Honoraria|Chiesi: Grant/Research Support|Chiesi: Honoraria|CSL Behring: Grant/Research Support|CSL Behring: Honoraria|Fresenius: Grant/Research Support|Fresenius: Honoraria|Hansa: Grant/Research Support|Hansa: Honoraria|Hexal: Grant/Research Support|Hexal: Honoraria|Hookipa Biotech: Grant/Research Support|Hookipa Biotech: Honoraria|Merck Sharp & Dohme: Grant/Research Support|Merck Sharp & Dohme: Honoraria|Novartis: Grant/Research Support|Novartis: Honoraria|Otsuka: Grant/Research Support|Otsuka: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria|Roche: Grant/Research Support|Roche: Honoraria|Sandoz: Grant/Research Support|Sandoz: Honoraria|Shire: Grant/Research Support|Shire: Honoraria|Siemens: Grant/Research Support|Siemens: Honoraria|Takeda: Grant/Research Support|Takeda: Honoraria|Veloxis: Grant/Research Support|Veloxis: Honoraria|Vitaeris: Grant/Research Support|Vitaeris: Honoraria Atul Humar, MD, MSc, FRCPC, Merck: Advisor/Consultant|Merck: Grant/Research Support|Roche: Grant/Research Support|Takeda: Advisor/Consultant Julia Garcia-Diaz, MD, Astellas Pharma US, Inc.: Advisor/Consultant|Astellas Pharma US, Inc.: Speaker's Bureau Robert P. Carroll, BM BCh (Oxon), FRACP, DM (Oxon), Bristol Myers Squibb: Grant/Research Support|HANSA Biopharma: Advisor/Consultant Yoshihiko Murata, MD, PhD, Former employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,: Stocks/Bonds Valerie L. Teal, MS, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,: Current Employee|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,: Stocks/Bonds Christopher L. Gilbert, n/a, Current employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,: Stocks/Bonds Barbara A. Haber, MD, Current employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co.,: Stocks/Bonds.
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 | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,001 | 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) | 0,000 | 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 ».