Glofitamab in Combination with R-ICE Chemoimmunotherapy or as Monotherapy in Children and Adolescents with Relapsed/Refractory B-cell non-Hodgkin Lymphoma: Initial Safety and Efficacy Results from the Ongoing iMATRIX-GLO Study
Notice bibliographique
Résumé
Background: Relapsed/refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL) in children, adolescents, and young adults is very rare and remains an area of high unmet need. The current 1-year overall survival is <30% and the complete response (CR) rate following treatment with rituximab, ifosfamide, carboplatin and etoposide (R-ICE) chemoimmunotherapy is 19% (Burke, et al. Blood Adv 2023). New effective treatment regimens are needed. T-cell engagers have been prioritized for evaluation in pediatric populations (Pearson, et al. Eur J Cancer 2019). Glofitamab is a CD20xCD3 bispecific antibody that was recently approved as monotherapy for the treatment of adult patients with R/R diffuse large B-cell lymphoma after ≥2 lines of therapy; in these patients, glofitamab monotherapy induced high response rates with manageable safety (Dickinson, et al. N Engl J Med 2022). iMATRIX-GLO (NCT05533775) is a prospective, Phase I/II, open-label, single-arm, two cohort trial evaluating the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of glofitamab in combination with R-ICE (Glofit+R-ICE) in children and young adults (up to 30 years) with R/R B-NHL after one prior line of therapy (Cohort A) and as monotherapy in children (6 months to <18 years) with R/R B-NHL after ≥2 lines of prior therapy (Cohort B). Here, we report initial safety and efficacy data from the first six pediatric patients. Methods: Eligible patients had CD20+ R/R B-NHL, measurable disease, and adequate organ function. Informed consent was obtained prior to enrollment. Obinutuzumab pretreatment was administered prior to glofitamab step-up dosing. Patients treated with Glofit+R-ICE received up to three 21-day treatment cycles and those treated with glofitamab monotherapy were eligible to receive up to 12 cycles. Primary endpoints included achievement of a CR after up to three cycles of combination therapy (according to the International Pediatric NHL Response Criteria for pediatric patients and the Lugano classification for young adult patients), evaluation of glofitamab safety (cytokine release syndrome [CRS] events were graded by ASTCT criteria, other adverse events [AEs] by NCI CTCAE v5.0) and tolerability for the combination arm, as well as glofitamab PK for both arms. The study is open in 20 sites across eight countries; the first patient was enrolled in November 2022. Results: As of 8 April 2024,six children were enrolled in the study; median age was 15 years (range: 7-18). Five patients had Burkitt lymphoma and one had Burkitt leukemia. Three patients had R/R B-NHL and one prior line of therapy and received Glofit+R-ICE for up to three cycles. Three patients had R/R B-NHL and ≥2 prior lines of therapy and received glofitamab monotherapy for up to five cycles. All three patients who received Glofit+R-ICE achieved a CR, of whom two subsequently underwent hematopoietic stem cell transplantation (HSCT) and remained in remission up to 12 months post-transplant. One patient relapsed prior to reaching HSCT. All three patients who received glofitamab monotherapy had progressive disease. Overall, safety was manageable and similar to that observed in adults. CRS was the most common AE, reported in all six patients. Low-grade CRS occurred in four patients (Grade [Gr] 1, n=3; Gr 2, n=1), with high-grade CRS occurring in two patients (Gr 3, n=1; Gr 4, n=1) who received glofitamab monotherapy. All CRS events resolved. Hematological toxicities were the second-most frequently reported AEs, and included anemia, neutropenia, and thrombocytopenia. No fatal AEs were reported. No AEs led to discontinuation of glofitamab therapy. Conclusions: In this ongoing iMATRIX-GLO study, initial data showed encouraging efficacy for Glofit+R-ICE in three children with R/R B-NHL and one prior line of therapy, with all three patients achieving a CR. The overall safety of glofitamab in combination or as monotherapy was manageable and consistent with the safety profile observed in adults. Future data will further establish the safety and efficacy of glofitamab in pediatric patients with R/R B-NHL. Updated data will be presented.
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 | 0,001 | 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 | 0,002 |
| 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 ».