A Novel Anti-CD22 Immunotoxin, Moxetumomab Pasudotox (HA22, CAT-8015): Activity in Pediatric Patients with Relapsed Acute Lymphoblastic Leukemia (ALL) After Allogeneic Hematopoietic Stem Cell Transplantation (SCT)
Notice bibliographique
Résumé
Despite the curative potential of SCT for pediatric ALL, relapse remains the most frequent cause of treatment failure. Management of relapse after SCT is complicated by drug resistance, limited utility of DLI, treatment-related toxicities, and GVHD. Moxetumomab pasudotox (MP) is a recombinant anti-CD22 immunotoxin with properties that warrant evaluation in the peritransplant setting. Cytotoxicity is mediated by targeted inhibition of protein synthesis in CD22+ cells, an antigen expressed on most B-lineage ALL blasts, and no immune effector cells are required for activity. A pediatric phase I trial of MP is being conducted for CD22+ hematologic malignancies (ClinicalTrials.gov NCT00659425). Doses are administered at 5-40 μg/kg IV QODx6 every 21 days. An initial cohort (A) included 1 patient each at the first 3 dose levels followed by standard 3+3 dose escalation starting at 30 μg/kg. In an attempt to prevent capillary leak syndrome (CLS), an ongoing cohort (B) receives dexamethasone around MP doses. 23 patients have been treated to date. The most common drug-related adverse events (AEs) were mild, reversible increased weight, transaminase elevation, and hypoalbuminemia. Treatment was discontinued in 1 patient after dose 1 due to ALL-related complications. Dose-limiting CLS was observed in 2 patients in Cohort A (30 μg/kg; grade 3 and 4, deemed drug-related serious AEs) and in no patients in Cohort B. 1 patient treated at 40 μg/kg developed refractory hypercalcemia, that was possibly drug-related, and died of cardiac arrhythmia during central venous catheter placement. That dose level (5B) was expanded and is accruing. 12 of 23 patients had prior SCT for ALL. Time from SCT to relapse was 3-12 mos (median, 9) and from SCT to treatment with MP was 4-34 mos (median, 13). 9 of 12 patients who had previously undergone SCT were evaluable for response. 3 (33%) patients had complete responses (CR) and 4 (44%) had hematological activity (>50% blast reduction and/or improvement in neutrophil/platelet counts). 1 patient with a CR confirmed by flow cytometry proceeded to 2nd SCT. MP is active in relapsed pediatric ALL after SCT. Notably, 3 of 4 CRs observed so far on this trial have been in patients treated for post-transplant relapse. The observed antileukemic activity and safety profile of MP, coupled with its unique properties, warrant further study in the peritransplant setting.
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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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| 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 ».