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Enregistrement W4385667651 · doi:10.1097/01.hs9.0000971208.36694.eb

P1078: MOSUNETUZUMAB DEMONSTRATES DURABLE RESPONSES IN PATIENTS WITH RELAPSED AND/OR REFRACTORY FOLLICULAR LYMPHOMA WHO HAVE RECEIVED ≥2 PRIOR THERAPIES: UPDATED ANALYSIS OF A PIVOTAL PHASE II STUDY

2023· article· en· W4385667651 sur OpenAlexaff
Laurie H. Sehn, Nancy L. Bartlett, Matthew J. Matasar, Stephen J. Schuster, Sarit Assouline, John Kuruvilla, Mazyar Shadman, Chan Y. Cheah, Keith Fay, Matthew Ku, Loretta J. Nastoupil, Michael C. Wei, Shen Yin, Iris To, Nan Hu, Juliana Min, Elicia Penuel, Anton Belousov, Alexandre Coimbra, Skander Jemaa, Brendan C. Bender, David C. Turner, Lihua E. Budde

Notice bibliographique

RevueHemaSphere · 2023
Typearticle
Langueen
DomaineMedicine
ThématiqueCAR-T cell therapy research
Établissements canadiensPrincess Margaret Cancer CentreJewish General HospitalMcGill UniversitySpinal Cord Injury BCUniversity of British Columbia
Organismes subventionnairesnon disponible
Mots-clésMedicineFollicular lymphomaInternal medicineRefractory (planetary science)Clinical endpointPhases of clinical researchSurrogate endpointLymphomaClinical trialOncologySurgeryGastroenterology

Résumé

récupéré en direct d'OpenAlex

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Mosunetuzumab (Mosun) is a CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells. In a pivotal Phase II study (NCT02500407; GO29781), fixed-duration Mosun demonstrated a high rate of complete responses (CRs) and durable responses in patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL) and ≥2 prior lines of therapy. Mosun has a manageable safety profile, supporting its use in an outpatient setting (Bartlett et al. 2022). Aims: We report the efficacy outcomes for pts with R/R FL and ≥2 prior lines of therapy who achieved CR by the end-of-treatment (EOT), with a median follow-up of 28.6 months. Methods: Eligible pts with R/R FL (Grade [Gr] 1–3a) and ≥2 prior therapies were enrolled. All pts provided informed consent prior to study entry. Mosun was administered intravenously in 21-day cycles with step-up dosing in Cycle (C) 1 (C1 Day [D] 1, 1mg; C1D8, 2mg; C1D15/C2D1, 60mg; C3D1 and onwards, 30mg). Hospitalization for treatment was not required. Pts achieving CR by C8 completed treatment with no further cycles; pts with a partial response (PR) or stable disease received up to 9 further cycles (17 in total). The primary endpoint was IRC-determined CR rate (as best response; Cheson 2007 criteria). Exploratory analyses assessed the association between total metabolic tumor volume (TMTV) at baseline (BL), as a surrogate for tumor burden, and clinical efficacy and safety. TMTV was derived from PET images at study entry using an AI-based model (Jemaa et al. 2022). Results: Ninety pts with R/R FL and ≥2 prior therapies were enrolled. Of these, 54 pts (60%) achieved CR as best response: 49 pts (54%) achieved CR at EOT; 1 pt with a CR experienced disease progression (PD) in C8; and 4 pts achieved CR after EOT due to delayed bone marrow confirmation. In the 49 pts with CR at EOT, median age was 63 years (range: 29–90), 82% had stage III/IV disease, and median number of prior lines of therapy was 3 (range: 2–10). As of July 8, 2022, median time on study was 28.6 months. Among the 49 pts who achieved CR at EOT, median duration of CR (DOCR; INV-assessed) was not reached (NR); 24-month DOCR rate after first CR was 65% (95% CI: 39–90). Median progression-free survival (PFS) was NR; 24-month PFS rate was 77% (95% CI: 63–91; Table). Two years after the end of fixed-duration treatment, 67% of these 49 pts remained free of PD or death. Of the 54 pts with CR as best response, 33 pts achieved their first CR by the first mandatory tumor assessment at 3 (±0.5) months (early CR) and 21 pts achieved their first CR after the month 3 assessment (late CR), including 5 pts with a PR that converted to a CR after >8 cycles of treatment. Median duration of response (DOR) was NR in patients with an early or late CR. In pts with PR as best response (n=16), median DOR was 4 months (95% CI: 3–7). Median TMTV at BL (n=82) was 139cm3 (range: 0–4858). No correlation was observed between BL TMTV and best overall response. A higher rate of Gr ≥2 cytokine release syndrome (CRS; ASTCT 2019 criteria) events was observed in pts with bone or bone marrow metabolic disease burden (n=24) versus those without (n=58; 33% vs 14%, respectively). Summary/Conclusion: Fixed-duration Mosun monotherapy demonstrated a high CR rate at EOT in pts with R/R FL, with a high proportion remaining event-free 2 years after EOT. Exploratory analyses did not suggest an association between the timing of the first CR and DOR. TMTV at BL was not associated with response to Mosun; however, Gr ≥2 CRS events were more common in pts with bone or bone marrow metabolic disease burden versus those without.Keywords: Relapsed lymphoma, Non-Hodgkin’s lymphoma, Bispecific, Follicular lymphoma

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 enseignants

Ni 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.

score de la tête « metaresearch » (Codex)0,001
score de la tête « metaresearch » (Gemma)0,000
Version: codex-gemma-dda1882f352aStatut de validation: machine_predicted_unvalidated
Catégories candidatesCharge utile insuffisante (le modèle a refusé de juger)
Catégories consensuellesaucune
DomaineSignal candidat: aucune · Signal consensuel: aucune
Devis d'étudeSignal candidat: Observationnel · Signal consensuel: Observationnel
GenreSignal candidat: Empirique · Signal consensuel: Empirique
Score de désaccord entre enseignants0,064
Score d'incertitude au seuil0,999

Scores Codex et Gemma par catégorie

CatégorieCodexGemma
Métarecherche0,0010,000
Méta-épidémiologie (sens strict)0,0000,000
Méta-épidémiologie (sens large)0,0010,000
Bibliométrie0,0010,003
Études des sciences et des technologies0,0000,000
Communication savante0,0000,000
Science ouverte0,0000,000
Intégrité de la recherche0,0000,000
Charge utile insuffisante (le modèle a refusé de juger)0,0020,000

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.

Tête enseignante Opus0,022
Tête enseignante GPT0,310
Écart entre enseignants0,288 · la distance entre les deux têtes enseignantes sur ce seul travail
Statut de validationscore_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 découle

Classification

machine, non validée

Prédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.

Devis d'étudeObservationnel
Domainenon disponible
GenreEmpirique

Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».

En bref

Citations6
Publié2023
Routes d'admission1
Résumé présentoui

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