Long-term efficacy and safety of etentamig, a B-cell maturation antigen (BCMA) bispecific antibody in patients with relapsed/refractory multiple myeloma (RRMM).
Notice bibliographique
Résumé
7527 Background: Etentamig (etenta) is a differentiated BCMA x CD3 bispecific T-cell engager composed of high avidity bivalent BCMA-binding domains, low-affinity CD3-binding domain designed to reduce cytokine release syndrome (CRS), and silenced Fc tail for extended half-life enabling convenient dosing. We present long term results from 2 ongoing Ph 1 studies evaluating efficacy and safety of etenta in patients (pts) with RRMM. Methods: Data were from a Ph 1 multicenter, open-label, dose escalation/expansion (NCT03933735) trial and Arm A of a Ph 1b, open label (NCT05650632) trial of etenta; both enrolled pts ≥18 years with RRMM, ≥3 prior lines of therapy (LoT), and triple-class exposed. Pts received 60 mg Q4W or 40 mg Q3W, both regimens with similar dose intensity, in the Ph 1 trial; pts from Arm A of the Ph 1b trial received a step-up dose (SUD) on day 1 and full dose of 60 mg Q4W on day 4. This pooled analysis assessed long-term efficacy, safety, and tolerability. Tumor response was assessed per IMWG 2016 criteria. Results: Of 146 pts with RRMM who received etenta, 87 (60%) were male, median age (range) was 68 (40–87) years, median prior LoT were 4 (3–23), and median duration of follow-up was 13 (1–48) months (mo). ORR was achieved in 96 (66%) pts and ≥VGPR in 79 (54%) pts. Response rates across subgroups are reported in the Table. Median duration of response was not reached (NR) (NR–NR) among responders; Kaplan-Meier (KM) estimate at 12 mo was 71% (58.5%–80.5%). Median PFS (mPFS) was NR (8.7–NR) mo; KM estimate at 12 mo was 55% (44.9%–63.1%). Any grade and G3/4 treatment emergent adverse events (TEAEs) occurred in 145 (99%) pts and 116 (79%) pts. Most common G3/4 TEAEs (≥15%) were neutropenia (38%), anemia (23%), lymphopenia (25%), and thrombocytopenia (16%). Infections G3/G4 were reported in 32 (22%) pts; most common infections G3/G4 (≥5%) were pneumonia (12%) and sepsis (5%). TEAEs leading to etenta discontinuation were reported in 13 (9%) pts. Deaths from TEAEs were reported in 13 (9%) pts; 10 were not attributed to etenta treatment. In Arm A of Ph 1 study where 60mg Q4W was administered with SUD and modified dex as premedication, CRS incidence was 30% (4% G2; No ≥G3 events) with median time to CRS onset of 22.3 (5.5–29.6) hours; and median time to CRS resolution of 20.7 (1.8–131.7) hours. Conclusions: Etenta with SUD demonstrated a low CRS incidence, durable response, and tolerability in pts with heavily pretreated RRMM. Efficacy across all subgroups was comparable and maintained, suggesting therapeutic benefits among a broad population and supporting further exploration in the ongoing Ph 3 Cervino study. Subgroup ORR, n (%) ≥VGPR, n (%) mPFS, months (range) Age ≥75years 26 (72) 23 (63.9) NR (7.5–NR) Race: Black 15 (63) 13 (54.2) 13.7 (5.0–NR) High cytogenetic risk 21 (55) 18 (47.4) 7.4 (2.8–NR) 3 prior LoT 29 (64.4) 23 (51.1) 13.5 (5.6–NR) ≥4 prior LoT 67 (67) 56 (56) NR (8.3–NR)
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 | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».