Gain1q in Myeloma Randomized Clinical Trials- How Is It Reported and How Does It Impact Outcomes: A Systematic Review
Notice bibliographique
Résumé
Introduction: Extra copies of chromosome 1q21 (+1q: gain=3 copies, amp=4 or more copies) have been associated with worse outcomes for patients with multiple myeloma (MM). We performed a systematic review to evaluate current reporting of +1q, efficacy of existing regimens for +1q, and prognostic implications of +1q in MM randomized controlled trials (RCTs). Methods: We searched three databases for MM RCTs. Our inclusion criteria were all published MM RCTs from 2012-2022. Each MM RCT was analyzed for reported data on +1q. The following features specific to +1q were collected: +1q reported or not as a high-risk cytogenetic alteration, definition of gain1q with respect to percentage of cells with abnormality detected, documentation of distinction between Gain1q and Amp1q in analysis, prevalence of +1q in enrolled population, outcomes of patients [Overall Survival (OS) and Progression Free Survival (PFS)] in patients with +1q in the experimental versus control arm and in patients with and without +1q. Results: A total of 124 trials were included. Among these trials, 28 (23%) studies reported data on +1q, including 26 studies that reported data in the primary manuscript and two studies that reported in separate publication. These trials reported a total of 2692 patients with +1q which represented 25% of all the patients enrolled. Out of 28 trials, three trials (11%) specified the criteria for categorizing patients as +1q (example in IKEMA and IFM-99: the presence of at least three copies in at least 30% of analyzed plasma cells was required). Only four trials (14%) reported survival data on gain and amp separately and the remaining 24 (86%) studies reported for gain or did not specify gain vs amp. Amongst the trials that reported +1q, 22 (79%) considered this to be a high-risk cytogenetic abnormality. Amongst trials that met primary endpoint showing improvement in PFS and clearly reported on +1q, the following drugs also improved PFS for those with +1q (when comparing hazard ratio (HR) for intervention versus control arm in the +1q subgroup): lenalidomide (len) maintenance in Myeloma XI, selinexor in BOSTON, and isatuximab in IKEMA and ICARIA. Several trials met their endpoint and showed improvement in PFS in the +1q cohort in same direction as overall study results but had confidence intervals for +1q subgroup that crossed 1. These included addition of carfilzomib in Myeloma XI, addition of carfilzomib vs bortezomib to len and dex for +1q (but not in Amp1q) in ENDURANCE, addition of elotuzumab to pomalidomide and dex, and bortezomib-based treatment before and after autologous stem cell transplantation (auto-SCT) vs no bortezomib (Table 2). Seven studies reported HR for patients with +1q in the trial (across both arms) compared to those without. In six studies (all studies other than SWOG1211), worse outcomes were seen with respect to OS and PFS for those with +1q versus without (Table 2). Important interventions for which subgroup analysis of +1q was not presented in trial results, and hence conclusions about the efficacy of the drugs specifically for patients with +1q cannot be ascertained included pomalidomide and ixazomib. Although subgroup analysis of various daratumumab trials has shown improvement for high-risk MM, the effect on gain1q was not isolated. Two recent contemporary trials that isolated effect of auto-SCT (DETERMINATION and IFM-2009) did not report +1q. However, in FORTE Trial, adverse prognostic implications of +1q were not seen in the arm receiving carfilzomib, len, dex and auto-SCT, indicating a possible role of carfilzomib and auto-SCT in ameliorating the adverse prognostic implications of +1q. Although len maintenance improved PFS after auto-SCT as maintenance in Myeloma XI overall for those with +1q, it did not appear to improve PFS for patients with isolated +1q (with no other concurrent genetic abnormalities). Conclusion: This systematic review of MM RCTs finds considerable heterogeneity in the reporting of +1q abnormalities in the literature, and +1q to be inconsistently classified as a poor prognostic factor in subgroup analysis of randomized myeloma trials. Most interventions that have shown to be successful in randomized trials and have clearly reported on the +1q subgroup have shown concordant direction of results and benefit of the applied intervention in the +1q subgroup. A more standardized approach to reporting of this abnormality is needed.
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 | 0,051 | 0,240 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,002 |
| Méta-épidémiologie (sens large) | 0,019 | 0,014 |
| Bibliométrie | 0,009 | 0,010 |
| Études des sciences et des technologies | 0,001 | 0,002 |
| Communication savante | 0,005 | 0,006 |
| Science ouverte | 0,003 | 0,002 |
| Intégrité de la recherche | 0,004 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 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 ».