P385: COMPARISON OF CLINICAL OUTCOMES AND ADVERSE EVENTS IN OLDER ADULTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA TREATED WITH NATIVE VS PEGYLATED ASPARAGINASE
Notice bibliographique
Résumé
Background: Poor outcomes in older patients with acute lymphoblastic leukemia (ALL) result from the disease’s adverse biology and poor tolerance to chemotherapy due to organ dysfunction, frailty, and performance status. Pediatric-inspired chemotherapy protocols with asparaginase (ASP) have been used in our center over the past 20 years for patients >60 years old, initially, with native Escherichia coli asparaginase (EC-ASP), and later with pegylated E. coli (PEG-ASP). PEG-ASP has a longer half-life and potentially lower immunogenicity. The addition of asparaginase as a key treatment strategy for pediatric ALL is well recognized, but asparaginase treatment is also associated with notable adverse events (AEs) that increase with age, such as pancreatitis, thrombosis, and liver toxicity. Few studies have compared the safety and efficacy of PEG-ASP with EC-ASP in older adults with ALL. Aims: To compare the efficacy and AEs according to the type of ASP used, EC-ASP vs PEG-ASP, in patients >60 years old diagnosed with Philadelphia chromosome-negative (Ph-). Methods: All newly diagnosed patients >≥ 60 years old with Ph- ALL receiving chemotherapy with a modified pediatric-based regimen containing asparaginase between January 2002 and January 2022 were included. The treatment regimen consisted of induction, central nervous system prophylaxis, seven cycles of intensification, and 24 cycles of maintenance every 3 weeks. Of note, in the beginning, the PEG-ASP dose was adjusted based on trough serum ASP levels. Antimicrobial prophylaxis and thrombosis prophylaxis were generally used. Outcomes and AEs of patients that received PEG-ASP and EC-ASP were compared between two cohorts. Efficacy was assessed by complete remission (CR) rates, leukemia-free survival (LFS), and overall survival (OS). Results: A total of 73 patients were included, the median age was 67.5 (60-78) and 35 (47%) were males. 53 patients received EC-ASP and 21 PEG-ASP with no significant differences between groups. The median asparaginase dose in the EC-ASP group was 6205 IU/m2 (range 605 - 12825 IU/m2) and the median number of cycles was 7 (range 1-8). The median dose and number of cycles in the PEG-ASP group were 937IU/m2 (range 666-1087 IU/m2) and 6 (range 1-8) respectively. The median follow-up of the whole cohort among survivors was 54 months (32.5 vs 17 months for patients receiving EC-ASP and PEG-ASP, respectively). A total of 84% of the patients (n=62) completed the whole therapy plan with no differences between the type of ASP. Figure 1 summarizes and compares the rates of AEs. Thrombosis, transaminitis, hypofibrinogenemia, and pancreatitis were more frequent among patients who received PEG-ASP. There were no differences with respect to induction mortality rate (11%, n=8), CR rate after induction (80%, n=58), and rate of allogeneic hematopoietic stem cell transplant in first remission (8%, n=6) among the two groups. The estimated median OS was 56 months. Patients who received PEG-ASP vs EC-ASP did not have differences in terms of LFS and OS. Summary/Conclusion: Our dataset shows that both forms of ASP can be delivered to patients above 60 years with no difference in induction-related mortality, LFS, and OS. Higher rates of AEs with PEG-ASP warrant careful monitoring of these patients. To note there was an imbalance toward higher use and longer follow-up of patients that received EC-ASP and serum asparaginase activity was not broadly assessed. Further investigating approaches to manage dose reduction, the balance between drug dose and AEs, and the value of therapeutic drug monitoring will be pursued in the future to optimize therapy in this subgroup of patients.Keywords: Elderly, ALL, Acute lymphoblastic leukemia, Chemotherapy
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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) | 0,001 | 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 | 0,000 |
| 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.
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