Influence of different asparaginase formulations in the prognosis of children with acute lymphocytic leukaemia in Brazil: a multicentre, retrospective controlled study

Abstract

Summary Our group recently showed that the (ASNase) formulation available in Brazil from 2017 to 2018 when used at the same dose and frequency as the formulation provided previously did not reach the activity considered therapeutic. Based on these, our goal was to assess the impact of these facts on the prognosis of children with ALL at different oncology centers. A multicentre retrospective observational study followed by a prospective follow‐up. Patients aged >1 and <18 years in first‐line treatment followed up at 10 referral centres, between 2014 and 2018 who received the formulation Leuginase® were identified (Group B). For each patient, the centre registered 2 patients who received ASNase in the presentation of Aginasa® exclusively (Group A). Data collection was registered using (Redcap®). A total of 419 patients were included; 282 in Group A and 137 in B. Group A had a 3‐year OS and EFS of 91·8% and 84·8% respectively, while Group B had a 3‐year OS of 83·8% (P = 0·003) and EFS of 76·1% (P = 0·008). There was an impact on 3‐year OS and EFS of children who received a formulation. This result highlights the importance of evaluating ASNase and monitoring its activity.

Activity and toxicity of intramuscular 1000 iu/m2 polyethylene glycol‐E. coliL‐asparaginase in the UKALL 2003 and UKALL 2011 clinical trials

“…Of note, introduction of PEG-EcASNase in UKALL 2003 was considered a key contributor to improved survival outcomes observed in the trial. 18 Equally, inadequate exposure to ASNase, either from premature discontinuation due to toxicity, 34 silent inactivation 37 or treatment with a substandard product, 38 has been reported to be associated with poorer outcomes. 1 The use of generalised estimating equations to examine the influence of covariates on serial measurements allowed identification of age and treatment phase as factors that independently influenced ASNase activity in the UKALL substudies.…”

“…Of note, introduction of PEG‐EcASNase in UKALL 2003 was considered a key contributor to improved survival outcomes observed in the trial 18 . Equally, inadequate exposure to ASNase, either from premature discontinuation due to toxicity, 34 silent inactivation 37 or treatment with a substandard product, 38 has been reported to be associated with poorer outcomes 1 …”

Comment on: Unsatisfactory quality of E. coli asparaginase biogenerics in India: Implications for clinical outcomes in acute lymphoblastic leukaemia

“…2 Unfortunately, sequentially, we observed that this fact had a negative impact on event free survival and overall survival. 3 In the present study, Sidhu et al showed that none of the seven biogeneric formulations of native asparaginase marketed in India met the minimum manufacturing quality standards required for these products. 4 In a similar manner, Sankaran et al analyzed nine generic formulations of L-asparaginase.…”

Somatic FOXC1 insertion mutation remodels the immune microenvironment and promotes the progression of childhood acute lymphoblastic leukemia

“…With the continual improvements in the diagnosis and treatment of ALL in children, and the application of multi-drug combination therapy, supportive therapy and hematopoietic stem cell transplantation, the 5-year disease-free survival rate of ALL in children exceeds 80–90%, thus making it a curable malignant tumor [ 5 , 6 ]. However, a considerable number of patients with ALL death because of complications and recurrence of chemotherapy [ 7 ]. An in-depth study of the pathogenesis of ALL in children would provide a solid theoretical basis for the discovery of new biological markers and new targeted therapeutic sites, as well as a new diagnostic basis for ALL in children.…”