Lower incidence of clinical allergy with PEG‐asparaginase upfront versus the sequential use of native E. coli asparaginase followed by PEG‐ASP in pediatric patients with acute lymphoblastic leukemia

Abstract

Asparaginase (ASP) is an essential component for the acute lymphoblastic leukemia (ALL) treatment, but toxicities, such as allergy, frequently limit its use. Although the potentially lower PEG-ASP formulation immunogenicity, few studies with conflicting results have compared the allergy incidence between Escherichia coli-ASP and PEG-ASP in the same protocol. We aimed at comparing the allergy incidence in children receiving native E. coli-ASP versus PEG-ASP within the same clinical protocol (Spanish Society of Pediatric Hematology and Oncology ALL-SEHOP-PETHEMA 2013). One hundred and twenty-six children (1-19 years) diagnosed with ALL from 2013 to 2020 were included. Patients in group 1 received a sequential scheme of native E. coli-ASP 10,000 IU/m 2 intramuscularly (IM) followed by PEG-ASP 1000 IU/m 2 IM. Patients in group 2 received PEG-ASP 1000 IU/m 2 IM upfront. Clinical allergy incidence was compared between both groups. Serum ASP activity (SAA) was measured in a subgroup of patients, and silent inactivation was recorded. The cumulative incidence of clinical allergy was significantly higher in group 1 (native followed by PEG-ASP) than in group 2 (PEG-ASP upfront), 24.7% versus 4.1% (p = 0.0085). Adequate ASP activity was achieved with PEG-ASP 1000 IU/m 2 dose in most patients (median SAA 412.5 and 453.0 IU/L at days 7 and 14).

Native E. coli asparaginase upfront should be replaced by PEGasparaginase upfront in the treatment of pediatric patients with acute lymphoblastic leukemia

“…When using IM, which is the normal usual way of asparaginase administration in Spain, this is associated with more anxiety in the patients. 8 In line with the previous reports using PEGasparaginase upfront in children with newly diagnosed ALL is also supported by the data of Mesegué et al 10 all part figures (A, B, and C). The R lme (linear mixed effects models) function of the nlme (nonlinear mixed effects models) package was used to perform statistical analysis on these data, https://CRAN.R-project.org/package=nlme, R package version 3.1-152.…”

“…A lower asparaginase dosage could lead to less toxicity, 12 this was already suggested by Tong et al when using PEGasparaginase IV. 13 Mesegué et al 10 performed linear mixed models, this is in general in line with the analysis of Tong et al 13 In the original pub- Ammonia (Figure 1A) and triglyceride levels (Figure 1B) were associated with the asparaginase activity levels, however for triglyceride this association was not significant (p = 0.084) and significantly different for ammonia (p = 0.013). 14 Also, we found a negative association between albumin (Figure 1C) and asparaginase activity levels (p < 0.0001), which is in line with a recent report.…”

“…9 This is an important conclusion as Mesegué et al conducted a meaningful clinical study, and they concluded that PEGasparaginase used upfront was associated with a lower incidence of a clinical allergy to PEGasparaginase. 10 This is consisted with the recent results of Kloos et al 4 Mesegué et al analyzed one hundred and twenty-six children (not including infants) who were diagnosed with ALL from 2013 to 2020. 10 This study is quite interesting and also a novel one as two different treatment regimens were compared within the same ALL protocol.…”

Venous thromboembolism in pediatric patients with acute lymphoblastic leukemia under chemotherapy treatment. Risk factors and usefulness of thromboprophylaxis. Results of LAL‐SEHOP‐PETHEMA‐2013

“…The protocol treatment is a BFM‐based trial published previously 27 and consisted of a four‐drug induction phase (IA), followed by induction IB, consolidation, reinduction, and maintenance in standard‐ and intermediate‐risk groups. High‐risk groups received three intensive chemotherapy blocks, three reinduction cycles, and maintenance.…”

Asparaginase drugs: a new view of the mechanism of action, side effects and experience in BFM (Berlin–Frankfurt–Munster) protocols

“…В настоящее время идентифицировано 3 вида антител к L-АСП: непосредственно к ферментной части лекарственного препарата, к полиэтиленгликолю (ПЕГ-части) и SS-линкеру, который соединяет субстрат фермента, и ПЕГ. При развитии реакции гиперчувствительности в фазу индукции ремиссии при ОЛЛ в большинстве случаев антительный ответ опосредован ПЕГ-частью препарата и SS-линкером, в то время как ответ в фазу интенсификации обусловлен выработкой антител преимущественно к ферментной части L-АСП [18,30,[32][33][34].…”