Post Autologous Stem Cell Transplant Maintenance in Patients with Newly Diagnosed Multiple Myeloma: A Network Meta-Analysis
Notice bibliographique
Résumé
Introduction The therapeutic paradigm for newly diagnosed multiple myeloma (NDMM) patients undergoing autologous stem cell transplant (ASCT) is evolving. Emergence of newer maintenance therapies has prompted this network meta-analysis to assess the comparative effectiveness of available options using the most up-to-date evidence, and thereby informing optimal therapy in this setting. Methods MEDLINE and EMBASE were comprehensively searched using a systematically structured search strategy to identify phase II/III randomized controlled trials (RCTs) assessing contemporary maintenance therapies in NDMM patients undergoing ASCT. The main outcomes of interest included progression-free survival (PFS) and overall survival (OS). Precomputed hazard ratios (HR) with 95% CI were pooled using an inverse variance approach. Incidence rate ratios were computed for trials not reporting HR. Mixed treatment comparisons were made using a network meta-analytic approach within the frequentist framework. Relative treatment rankings were evaluated using P-scores (PS) and were interpreted in congruency with pairwise estimates. Higher ranks indicated better efficacy. Results As of 25th July 2022, 16 RCTs with 12 unique treatment arms, and 14 RCTs with 10 unique treatment arms, contributed to the network of PFS and OS outcomes, respectively. Mixed treatment comparisons showed that the combination of carfilzomib, lenalidomide, and dexamethasone (KRd) and KR were associated with significantly improved PFS when compared to lenalidomide (Len) maintenance (KRd vs. Len - HR: 0.56; 95% CI: 0.34-0.93, KR vs. Len - HR: 0.64; 0.44-0.94), daratumumab (Dara) (KRd vs. Dara - HR: 0.53; 0.30-0.93, KR vs. Dara - HR: 0.60; 0.38-0.96), thalidomide-steroid (Thal-Steroid) (KRd vs. Thal-Steroid: HR - 0.49; 0.28-0.84, KR vs. Thal-Steroid - HR: 0.56; 0.36-0.86), Thal (KRd vs. Thal - HR: 0.40; 0.23-0.69, KR vs. Thal - HR: 0.46; 0.30-0.71), and ixazomib (Ixa) maintenance (KRd vs. Ixa - HR: 0.39; 0.22-0.68, KR vs. Ixa - HR: 0.44; 0.28-0.69). Although there was a signal of potential PFS benefit with KRd and KR when compared to Ixa, lenalidomide, and dexamethasone (IRd), the difference was not statistically significant (KRd vs. IRd - HR: 0.68; 0.34-1.32, KR vs. IRd - HR: 0.77; 0.43-1.39). The results were consistent for KRd and KR as compared to Len-Steroid (KRd vs. Len-Steroid - HR: 0.67; 0.36-1.23, KR vs. Len-Steroid - HR: 0.76; 0.45-1.28). However, KRd and KR were not significantly different from each other. Ranking analysis showed KRd (PS: 0.95; rank 1) and KR (PS: 0.91; rank 2) were potentially the most efficacious with regards to PFS benefit followed by IRd and Len-Steroid (PS: 0.75, rank 3), Len (PS: 0.63; rank 5), Dara (PS: 0.57; rank 6), Thal-Steroid (PS: 0.49; rank:7), Thal (PS:0.30; rank: 8), and Ixa (PS: 0.28; rank: 9). Len maintenance was associated with significantly improved PFS compared to Ixa (HR: 0.69; 0.55-0.88), and Thal (HR: 0.72; 0.59-0.88) as shown in Figure 1A. Mixed treatment comparisons for OS outcomes showed a consistent pattern of benefit with KR when compared to Thal (HR: 0.40; 0.19-0.86), Thal-Steroid (HR: 0.46; 0.21-0.99), and Len-Steroid (HR: 0.35; 0.13-0.94). Although, there is a signal of OS benefit with KR when compared to Len, the effect is not statistically significant (HR: 0.54; 0.26-1.12). Similarly, while the direction of effect indicated potential OS benefit with KRd as compared to Thal, Thal-Steroid, and Len-Steroid, the difference was not statistically significant. No statistically significant associations were observed for other mixed treatment comparisons with regards to OS at the current follow up of the included trials as shown in Figure 1B. Sensitivity analyses limited to phase III RCTs showed consistent results. Conclusions Maintenance therapy with KRd and KR may prolong PFS compared to other therapies including Len, Thal, Ixa, and Dara maintenance but not when compared to Len-Steroid and IRd. Overall survival data is still emerging and results at longer-follow up with subgroup analyses by age, prior response status, and cytogenetic risk profiles are warranted and may offer additional insights. Thus, a living systematic review is being maintained and these results will be updated as soon as new data becomes available. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal
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 | 0,023 | 0,035 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,010 | 0,047 |
| Bibliométrie | 0,005 | 0,005 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,003 | 0,001 |
| Science ouverte | 0,002 | 0,002 |
| Intégrité de la recherche | 0,002 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».