Anti-CD38-based quadruplet versus triplet induction regimens in transplant-ineligible newly diagnosed multiple myeloma: A systematic review and meta-analysis
Notice bibliographique
Résumé
Abstract Introduction Triplet induction therapy with either daratumumab, lenalidomide, and dexamethasone (D-Rd) or bortezomib, lenalidomide, and dexamethasone (VRd) has long been the standard of care for transplant-ineligible patients with newly diagnosed multiple myeloma (TIE-NDMM). In recent years, anti-CD38-containing quadruplet induction regimens have increasingly been adopted as frontline therapies, with studies indicating their potentials to enhance treatment responses and improve survival outcomes. This meta-analysis aims to evaluate the efficacy and safety of these quadruplet regimens as initial treatment for this population. Methods We conducted a comprehensive literature search across PubMed, Embase, and Cochrane databases from inception to April 30, 2025. Included studies consisted of randomized controlled trials (RCTs) comparing anti-CD38-based quadruplet induction regimens to triplet induction regimens among TIE-NDMM patients. Outcomes of interest were progression free survival (PFS), overall survival (OS), rates of minimal residual disease (MRD) negativity, rates of stringent complete response and complete response (sCR/CR), rates of very good partial response (VGPR) or better, overall response rates (ORR), rates of severe adverse events (SAEs), grade 3 to 4 infections, neutropenia and thrombocytopenia. Statistical analyses were performed using Review Manager version 5.4.1. Heterogeneity was assessed using Cochran's Q test and I² statistics. Results A total of six RCTs involving 2,023 patients were identified, with sample sizes ranging from 121 to 706 participants and median follow-up durations between 34 and 59.7 months. 1088 participants received quadruplet induction while 935 received triplet induction. The quadruplet regimens comprised an anti-CD38 monoclonal antibody (daratumumab or isatuximab), a proteasome inhibitor (bortezomib or carfilzomib), an immunomodulatory drug (lenalidomide) or alkylator (melphalan or cyclophosphamide), and a corticosteroid. Triplet regimens consisted of the same backbone without the anti-CD38 agent. Quadruplet induction regimens significantly improved PFS (HR 0.49, 95% CI 0.39-0.61, P<0.00001, I²=56%) and OS (HR 0.63, 95% CI 0.52-0.76, P<0.00001, I²=0%) compared to triplet regimens. Quadruplets were associated with enhanced rates of MRD negativity at a threshold of 10⁻⁵ (RR 1.97, 95% CI 1.29-2.99, P=0.002, I²=92%), rates of sCR/CR (RR 1.46, 95% CI 1.01-1.98, P=0.02, I²=90%) and VGPR or better (RR 1.33, 95% CI 1.10-1.61, P=0.003, I²=88%). ORR was similar between patients receiving quadruplets and triplets (RR 1.12; 95% CI 1.00-1.26, P=0.04, I²=86%). There was a slight increase in the rates of SAEs (RR 1.14, 95% CI 1.01-1.29, P=0.03, I²=17%) and grade 3 to 4 infections (RR 1.36, 95% CI 1.14-1.6, P=0.0004, I²=0%) associated with quadruplets. There were no significant differences in the rates of grade 3-4 neutropenia (RR 1.23, 95% CI 0.97-1.74, I²=87%) and thrombocytopenia (RR 0.99, 95% CI 0.86-1.14, I²=0%) between the two groups. A subgroup analysis of frail patients revealed that the benefits of quadruplet therapy extend to this population, with significant improvements in both PFS (HR 0.51, 95% CI 0.4-0.65, P<0.0001, I²=0%) and OS (HR 0.69, 95% CI 0.51-0.93, P=0.02, I²=0%). Conclusion Our study provides compelling evidence that anti-CD38-based quadruplet induction regimens are a more effective upfront treatment option compared to triplet regimens for TIE-NDMM patients, demonstrating improvements in PFS, OS, MRD negativity, rates of sCR/CR, and VGPR, with manageable safety concerns. While quadruplet regimens were associated with higher rates of SAEs and grade 3-4 infections, no significant differences were observed in the rates of grade 3-4 neutropenia or thrombocytopenia. Careful patient selection is essential to optimize outcomes and mitigate treatment-related toxicity.
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 | 0,011 | 0,025 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,020 | 0,030 |
| Bibliométrie | 0,006 | 0,007 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,003 | 0,002 |
| Science ouverte | 0,002 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 ».