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 group.

The adoption of pediatric-inspired regimens for the treatment of Ph-negative acute lymphoblastic leukemia (ALL) in adults has improved prognosis. However, the feasibility of these intensive regimens in older patients is limited, due to the increased incidence of therapy-related side effects, including those related to asparaginase. In this sub-analysis carried out by the Campus ALL network, 90 ALL patients aged 55 or more (median age 59 years) homogeneously treated in real-life according to the GIMEMA LAL1913 program, were analyzed to evaluate the feasibility and tolerability of pegaspargase (PEG-ASP) treatment. Among the 90 patients analyzed, 86 (96%) received PEG-ASP at least in one of the first two courses (C1-C2) of chemotherapy and were evaluated for toxicity and outcome. In detail, 51 patients received PEG-ASP in both courses and 35 in either C1 or C2. The most common adverse event was hepatic toxicity (HT), with 38% of patients experiencing any grade of HT at C1 (HT grade ≥ 3, 19%) and 23% at C2 (HT grade ≥ 3, 9%). Additionally, HT at C1 was the primary reason for withholding PEG-ASP at C2. Coagulopathy was the second most frequent toxicity (any grade of toxicity in 26% of patients at C1 and in 20% at C2). No deaths directly related to PEG-ASP therapy were reported. The CR rate after C1 and C3 was 94% and 93%, respectively. MRD negativity rate was 40% and 68%, respectively. The OS and DFS probability at 3 years was 54% and 47%, respectively. PEG-ASP administration in older ALL patients is feasible, but HT is a concern, being the major cause of PEG-ASP interruption. Therefore, a dose adjustment, according to age and concomitant comorbidities, is advisable to balance PEG-ASP efficacy with its toxicity.