Blinatumomab Associated Seizure Risk in Patients with Down Syndrome and B-Lymphoblastic Leukemia: An Interim Report from Children's Oncology Group (COG) Study AALL1731
Notice bibliographique
Résumé
Abstract INTRODUCTION Children with Down Syndrome (DS) and B-lymphoblastic leukemia (B-ALL) are at an increased risk of both relapse and treatment-related mortality, compared to those without DS. On COG study AALL1731 for de novo B-ALL, patients with DS and higher risk features (DS-High) are non-randomly treated with a regimen replacing intensive elements of conventional chemotherapy with three 28-day cycles of blinatumomab, with the combined goals of reducing toxicity and enhancing anti-leukemic efficacy. The DS-High group includes all NCI high risk (HR) patients; NCI standard risk (SR) patients with end-induction minimal residual disease positivity (>0.01%), unfavorable cytogenetics, CNS3 status, steroid pre-treatment, neutral cytogenetics with CNS2 status, or testicular disease. Neurotoxicity is a known risk of blinatumomab, with an incidence of 4% in block 1 and 1% in block 2 among pediatric patients with relapsed ALL (Brown et al, JAMA 2021). However, the specific risk in patients with DS has not been described to date. Here, we provide an early report of increased seizure incidence associated with blinatumomab in older DS-High patients enrolled on AALL1731 to date. METHODS We reviewed seizure incidence among patients with DS enrolled on AALL1731 from June 2019 to June 2021 who had proceeded to receive blinatumomab. Blinatumomab was administered at a dose of 15 mcg/m 2/day, using dexamethasone pre-medication in cycle 1. Infusions were interrupted for seizures, with resumption at 5 mcg/m 2/d permitted following full resolution for grade 1-3 seizures. RESULTS Among DS NCI HR patients, 8 of 47 (17%) had a seizure during blinatumomab infusion (Table 1). All 8 seizures occurred in patients over 10 years old. Six of the 8 seizures occurred in the first cycle of blinatumomab, most in the first 3 days of the infusion. Four had concomitant fever or cytokine release syndrome. Seizures were grade 2 (n=2) or grade 3 (n=6), and all resolved with full neurologic recovery. Of the 8 patients, 5 elected to resume blinatumomab; no further seizures occurred in these patients. There was no indication of increased seizure risk among NCI SR DS-High patients (1 seizure among 11 patients), or among DS or non-DS patients receiving blinatumomab on other study strata (0 of 7 DS SR-Avg; 1 of 146 non-DS SR-Avg; and 2 of 120 non-DS SR-High). CONCLUSIONS The incidence of seizures associated with blinatumomab in DS-ALL patients older than 10 years appears higher than previously reported in children without DS. The majority of seizures occurred within the first 3 days, all fully resolved with no sequelae, and no patient who resumed blinatumomab infusion at a lower rate experienced further seizures. Seizure prophylaxis may be advisable in DS patients while receiving blinatumomab, particularly those >10 years of age. Further follow-up and a larger sample size are needed to confirm incidence and identify risk factors predisposing DS patients to neurologic toxicity. Figure 1 Figure 1. Disclosures Li: Novartis Canada: Membership on an entity's Board of Directors or advisory committees. Raetz: Pfizer: Research Funding; Celgene: Other: DSMB member. Loh: MediSix therapeutics: Membership on an entity's Board of Directors or advisory committees. Gupta: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Rau: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; AbbVie Pharmaceuticals: Other: Spouse is employee and stock holder; Servier Pharmaceuticals: Consultancy. OffLabel Disclosure: This trial includes the use of blinatumomab in combination with chemotherapy for treatment of de novo B-lymphoblastic leukemia.
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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 | 0,001 | 0,001 |
| 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 | 0,001 |
| 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 ».