First report of the GIMEMA INO-first multicenter observational study analyzing infective and non-infective complications in patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with inotuzumab ozogamicin.
Notice bibliographique
Résumé
Abstract INTRODUCTION. Based on the results of the phase III study INO-VATE, Inotuzumab ozogamicin (INO) has been approved as single agent for the treatment of adult patients with relapsed/refractory CD22 positive B-cell acute lymphoblastic leukemia (B-ALL) and for adult patients with Philadelphia positive (Ph+) ALL who previously failed the treatment with at least one TKI inhibitor. However, even if INO is extensively used in clinical practice, very few real-life data are available regarding the toxicity profile of this drug. METHODS. We report preliminary data from GIMEMA-INO-FIRST trial, a retrospective, observational clinical-epidemiological study (ClinicalTrials.gov ID NCT06025682). The study collects data from about 20 Hematologic Centers of the GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) Group treating B-ALL patients with inotuzumab-ozogamicin (INO) over the last 5 years (2018-2023), according to the authorized indications and not included in interventional clinical trials (randomized or not randomized). The main objective of this study is to analyze, in a real-life setting, the infective and non-infective adverse events (AEs) in patients with B-ALL treated with salvage INO immunotherapy. The AEs have been graded on a scale of 1 to 5 according to the Common Toxicity Criteria for AEs (CTCAE) Version 5.0. RESULTS. A total of 115 patients were enrolled in the study, of whom 98 (males 63%) are currently evaluable for this preliminary analysis. The median age was 57 years (range, 21–80 years), and 78% of patients had a performance status of 0 or 1. The 77% of cases had a relapsed and 23% a refractory B-ALL. The median pre-INO bone marrow (BM) blasts was 35%. Ph-positive ALL cases were 34% (33/98). INO was administered at the standard dose according to the data sheet, and most patients (80%) received two or more cycles (C) of INO. The overall response rate (ORR) to INO therapy was 66%, with a complete response (CR) rate of 63%. Death during INO treatment was only 2% and treatment discontinuation due to toxicity occurred in only 2 cases (2.8%). Of the 98 patients who received INO, 45 (46%) received a subsequent allogeneic transplantation-SCT (donor: sibling 27%, haplo 31%, MUD 42%). A total of 13 Grade > 2 AEs were reported during INO treatment (6 in C1, 5 in C2, 1 in C3, and 1 in C4) that occurred in 8.2% (8/98) of patients. Specifically, the following grade 2 or more AEs were reported: 3 FUO (3/3 grade 2), 3 pancytopenia (2/3 grade 3 and 1/3 grade 4), 2 intestinal mucositis (1/2 grade 2 and 1/2 grade 3), 1 pneumonia (grade 3), 1 pancreatic toxicity (grade 3), 1 hepato-renal syndrome (grade 4), 1 liver toxicity (grade 2), and 1 oral mucositis (grade 2). After SCT, a VOD was reported in 19% of cases (8/45). CONCLUSIONS. These preliminary data, which will undergo thorough analysis in the coming months, showed that significant (grade 2 or higher) infectious and non-infectious AEs were uncommon in patients with relapsed or refractory B-ALL who received INO salvage therapy. These AEs occurred in only 8.2% of patients and resulted in treatment discontinuation in only 2.8% of cases. These findings support the use of INO as a suitable bridging therapy to SCT or to other cellular immunotherapies.
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 | 0,003 | 0,006 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».