C049 | PEGASPARGASE ADMINISTRATION AND TOLERABILITY IN PATIENTS AGED 55 YEARS OR OLDER WITH ACUTE LYMPHOBLASTIC LEUKEMIA TREATED WITH THE LAL1913 PROGRAM. A SUBANALYSIS OF THE CAMPUS ALL-LAL1913 STUDY.

Introduction: The adoption of pediatric-inspired regimens for adult Ph-negative ALL improved the prognosis of this disease. However, the feasibility of these programs in older pts is limited due to the increased incidence of therapy-related AE, especially those related to asparaginase. Very few real-life data regarding the tolerability of pegaspargase (PEG-ASP) in older pts are available. Methods: In this sub-analysis of the CAMPUS ALL-LAL1913 study (Lazzarotto et al, Haematologica 2025) we analyzed 90 patients aged ≥55, treated according to the GIMEMA LAL1913 program in real life. The objectives were to describe the feasibility and tolerability of PEG-ASP in a uniformly treated population of older pts, with particular attention to PEG-ASP related toxicities and dose modulation in the first two courses of chemotherapy. Results: Overall 86/90 pts (96%) received PEG-ASP in at least one of the first two courses. Median age was 59 years (55-71), 12% were older than 65. Liver disease was found in 10% of pts and 5% were obese. Overall, 81/90 (90%) pts received PEG-ASP at C1. On medical decision and according to GIMEMA recommendations for PEG-ASP dose reduction, 67% pts received the standard dose of 1000 UI/m², 13% received a higher dose (median 1500 UI/m²) and 20% received a lower dose (median 500 UI/m²). C2 was administered to 77/90 (86%) pts and 56/77 (73%) received PEG-ASP (70% at standard dose, 7% at a higher dose, and 23% at a lower dose). At C1 hepatic toxicity occurred in 38% of pts (grade ≥3, 23%), coagulopathy in 26% (grade ≥3, 6%), thrombotic or hemorrhagic events in 7%, metabolic toxicity (dyslipidemia or hyperglycemia) in 11%, pancreatic toxicity in 4%. At C2 hepatic toxicity occurred in 23% of pts. Hepatic toxicity at C1 was the main reason to avoid PEG-ASP at C2. PEG-ASP was administered at a significantly reduced dose in older pts and in those with hepatic comorbidity. No deaths directly related to PEG-ASP therapy were reported. CR rates after C1 and C3 were 94% and 93% and MRD-negativity rates were 40% and 68%, respectively. The 3-year OS and DFS were 54% and 47%. Conclusions: PEG-ASP administration in intensively treated older ALL pts was feasible, but hepatic toxicity is a concern, particularly at C1 (grade 3 hepatic toxicity in 23% of pts). A careful evaluation of the patient’s comorbidities is important to identify those at higher risk of toxicity and a proper dose adjustment is very important to balance treatment efficacy with its toxicity.