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.
Year: 2025
Type: article
Abstract: 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.
Authors: D. Lazzarotto, A.M. Testi, M. Fanin, F. Mosna, S. Chiaretti, C. Papayannidis, A. Curti, M. Piccini, N. Fracchiolla, M. Fumagalli, P. Zappasodi, S. Imbergamo, P. Minetto, F. Guolo, F. Lussana, M. Cerrano, F. Forghieri, M. Leoncin, M. Olivi, M. Lunghi, S. Trappolini, C. Mazzone, M. Defina, L. Aprile, C. Pasciolla, M. Ciccone, E. Mauro, A. Mulè, F. Grimaldi, B. Cambò, L. Santoro, M. Delia, V. Mancini, A. Cignetti, R. Fanin, M. Bonifacio, M. Dargenio, F. Ferrara, G. Pizzolo, R. Foà, A. Candoni
Institutions: Azienda sanitaria universitaria Friuli Centrale, Sapienza University of Rome, University of Udine, Azienda Sanitaria dell'Alto Adige, Istituto di Ematologia di Bologna, Azienda Ospedaliero-Universitaria Careggi, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Policlinico San Matteo Fondazione, University of Padua, Ospedale Policlinico San Martino, University of Genoa, Ospedale Papa Giovanni XXIII, Azienda Ospedaliero-Universitaria di Modena, Ospedale dell' Angelo, Azienda Ospedaliera Citta' della Salute e della Scienza di Torino, Università degli Studi del Piemonte Orientale “Amedeo Avogadro”, Azienda Ospedaliero-Universitaria delle Marche, St. Eugenio Hospital, Azienda Ospedaliera Universitaria Senese, Azienda Ospedaliera S.Giuseppe Moscati, Arcispedale Sant'Anna, Ca' Foncello Hospital, Ospedale Vincenzo Cervello, Federico II University Hospital, University of Naples Federico II, University of Parma, Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, A. O. Ordine Mauriziano di Torino, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Ospedale Vito Fazzi, Ospedale Antonio Cardarelli
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7094976856
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