P32 MAJESTEC-1: CORRELATIVE ANALYSES OF TECLISTAMAB, A B-CELL MATURATION ANTIGEN (BCMA) X CD3 BISPECIFIC ANTIBODY, IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM)
Notice bibliographique
Résumé
Introduction: Teclistamab, a BCMA bispecific IgG4 antibody, redirects CD3+ T cells to mediate T cell activation and subsequent BCMA-expressing myeloma cell lysis. MajesTEC-1, a multicohort, open-label, phase 1/2 study, investigated teclistamab safety/efficacy in patients (pts) with RRMM previously receiving ≥3 lines of therapy. In phase 1, recommended phase 2 dose (RP2D) of teclistamab was 1.5mg/kg subcutaneous (SC) once weekly, preceded by 0.06 and 0.3mg/kg step-up doses. Initial results of RP2D-treated pts in phase 1/2 (no prior BCMA-targeted treatment exposure) demonstrated teclistamab was well tolerated with encouraging efficacy. Here, we report translational research data from MajesTEC-1 of the pivotal RP2D and active dose pt cohorts. Methods: Baseline/on-treatment whole blood and bone marrow aspirate samples from pivotal RP2D pts (SC) were analyzed by flow cytometry for BCMA expression/immune populations; serum samples were analyzed for soluble BCMA (sBCMA) by electrochemiluminescence ligand binding, and cytokines by MSD/Luminex assays; whole blood from active dose cohorts (intravenous/SC) was analyzed by cytometry by time of flight (CyTOF). Results: Baseline BCMA expression on bone marrow plasma cells was prevalent and highly variable among pts with RRMM but not associated with clinical responses to teclistamab; higher baseline sBCMA levels associated with lower response rates and high-risk disease characteristics (higher revised International Staging System stage, high bone marrow plasma cells [>60%], extramedullary plasmacytoma presence). Nonresponders had lower peripheral CD8 T cell counts, higher regulatory T cells (Tregs) and CD38+ Tregs, higher overall T cells expressing PD-1, TIM-3, CD38 in peripheral blood and bone marrow at baseline. Baseline analysis also showed enhancement of a naïve phenotype in T cells in responders. Higher baseline T cells expressing PD-1, TIM-3, CD38, CD25, PD-1/TIM-3, PD-1/CD38 observed in blood and bone marrow of pts with high bone marrow plasma cells (>60%), high composite tumor score (plasmacytosis ≥80%, serum M-spike ≥5g/dL, serum free light chain ≥5000 mg/L). Shorter progression-free survival (PFS) was associated with higher peripheral PD-1+ CD8 and baseline Tregs. Higher baseline CD25+ CD4, CD38+ CD4 bone marrow T cells correlated with lower PFS after tumor burden adjusting. Baseline T cell profile associated with worse clinical outcome likely reflects dysfunctional and exhausted T cell phenotype. Accordingly, lower interferon-g and PD-1+ CD8, CD25+ CD4, CD38+ CD4 T cell induction was observed with teclistamab treatment (nonresponders); teclistamab-mediated induction of peripheral PD‑1+ CD38+ CD8 T cells lower in pts with high tumor burden. Cytokine release syndrome was associated with higher CD3 T cells and lower baseline sBCMA, TIM-3, PD-1/TIM-3 expressing CD4 T cells in the periphery. Conclusions: Baseline correlative analysis for pivotal RP2D pts suggests emerging profile for nonresponders of unfavorable baseline immune characteristics, including lower T cell numbers, higher baseline T cells expressing PD-1, TIM-3, CD38, increased Tregs and CD38+ Tregs, and lower proportion of naïve T cells. These data support clinical combinations of teclistamab with agents like daratumumab or checkpoint inhibitors.
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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 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 ».