“upfront use of blinatumomab in adolescents and adults with Philadelphia Chromosome–Negative B-cell acute lymphoblastic leukemia: A systematic review and proportional meta-analysis”
Notice bibliographique
Résumé
Abstract Background: Philadelphia chromosome–negative (Ph–) ALL is a genetically heterogeneous entity defined by recurrent cytogenetic and molecular aberrations that shape its clinical trajectory and prognosis. Historically poor outcomes in adults prompted significant changes in therapeutic approaches over the past decade, resulting in improved survival. Currently, blinatumomab is a bispecific T-cell engager targeting CD19 in leukemic cells and CD3 on T Lymphocytes. It has shown significant results in relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, its role in the frontline treatment of Philadelphia chromosome–negative (Ph–) B-ALL, particularly in combination with chemotherapy, is continuously being explored. Objective: Our purpose is to evaluate the efficacy of blinatumomab-based frontline regimens in adolescents and adults with newly diagnosed Ph– B-ALL through a systematic review and meta-analysis of proportions. Methods: We systematically searched PubMed, Embase, and Cochrane from inception through May 2025. Eligible studies included adolescents or adults with a cut off age of 15 years old, with newly diagnosed Ph– B-ALL where blinatumomab was used in the induction phase, consolidation phase, or both. Primary outcomes were complete remission (CR), measurable residual disease (MRD) negativity, and 3-year overall survival (OS). Random-effects proportional meta-analyses were conducted using logit or Freeman–Tukey transformations. Risk of bias was assessed using RoB 2 for Randomized Controlled Trials and ROBINS-I for prospective trials. Subgroup analysis was performed, dividing subgroups by phase of Blinatumomab utilization; either induction, consolidation or both. To tackle heterogeneity in the MRD pooled results, we conducted a Meta-regression to evaluate the link between different treatment phases and sample sizes. Results: Thirteen studies (n = 878 patients) met the inclusion criteria. The pooled CR rate after induction-phase blinatumomab was 78% (95% CI: 71–85%; I² = 21.2%). The pooled MRD negativity rate was highest in the induction-only group, at 90% (95% CI: 83%–95%), with no significant heterogeneity (I² = 0%). The consolidation group showed a pooled MRD negativity rate of 88% (95% CI: 75%–96%), though heterogeneity was substantial (I² = 74.2%, p = 0.0087). For patients treated during both induction and consolidation, the pooled MRD negativity rate was 89% (95% CI: 82%–94%), also with no observed heterogeneity (I² = 0%). The overall pooled MRD negativity rate across all ten studies was 89% (95% CI: 84%–93%), using a random-effects model with Freeman–Tukey double arcsine transformation. A meta-analysis of four studies reporting 3-year overall survival (OS) following frontline blinatumomab-based therapy was performed, stratified by treatment phase. In the consolidation subgroup, the pooled 3-year OS was 83% (95% CI: 76%–88%), with no heterogeneity (I² = 0%, p = 0.4032). In contrast, for patients treated during both induction and consolidation, the pooled 3-year OS was 52% (95% CI: 22%–81%), with substantial heterogeneity (I² = 88.6%, p < 0.0001). Conclusions: Blinatumomab-based regimens in the frontline setting are associated with high MRD clearance and complete remission rates, particularly when used during induction or consolidation. However, the predominance of non-randomized studies, small sample sizes, and heterogeneity in MRD assessment limit definitive conclusions. Prospective randomized trials are needed to clarify the optimal integration of blinatumomab in frontline Ph– B-ALL therapy.
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 | 0,009 | 0,020 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,016 | 0,036 |
| Bibliométrie | 0,005 | 0,006 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,003 | 0,002 |
| Science ouverte | 0,002 | 0,002 |
| Intégrité de la recherche | 0,002 | 0,002 |
| 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 ».