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Pegaspargase (PEG-asparaginase)
Source: Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: April 21, 2025 · Captured 2026-09-09.
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Pegaspargase is a form of L-asparaginase in which the E. coli–derived enzyme is modified by the covalent attachment of polyethylene glycol. It is commonly used during both induction and postinduction phases of treatment in newly diagnosed patients treated in Western Europe. Pegaspargase is not available in the United States, but it is still available in other countries.
Pegaspargase may be given either intramuscularly (IM) or intravenously (IV).[11] Pharmacokinetics and toxicity profiles are similar for IM and IV pegaspargase administration.[11] There is no evidence that IV administration of pegaspargase is more toxic than IM administration.[11-13]
Pegaspargase has a much longer serum half-life than native E. coli L-asparaginase, producing prolonged asparagine depletion after a single injection.[14]
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Serum asparaginase enzyme activity levels of more than 0.1 IU/mL have been associated with serum asparagine depletion. Studies have shown that a single dose of pegaspargase given either IM or IV as part of multiagent induction results in serum enzyme activity of more than 0.1 IU/mL in nearly all patients for at least 2 to 3 weeks.[11,12,15,16] In one study of 54 NCI high-risk patients conducted by the COG, plasma asparaginase activity as low as 0.02 IU/mL was associated with serum asparagine depletion. Using that cutoff value, it was estimated that 96% of patients maintained the therapeutic effect (plasma asparagine depletion) for 22 to 29 days after a single pegaspargase dose of 2,500 IU/m2.[17] In one randomized study, higher doses of pegaspargase (3,500 IU/m2) did not improve outcome when compared with standard doses (2,500 IU/m2).[18][Level of evidence A1]
In another study, doses of pegaspargase were reduced in an attempt to decrease toxicity.[19] While lower doses were successful in maintaining appropriate asparaginase levels of more than 0.1 IU/mL, the frequency of asparaginase-related toxicities was similar to the frequency of toxicities reported in previous studies that used higher doses of pegaspargase. This study did not report on the impact of lower doses of pegaspargase on EFS.
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Evidence (use of pegaspargase versus native E. coli L-asparaginase):
A randomized comparison of IV pegaspargase versus IM native E. coli asparaginase was conducted. Each agent was administered for a 30-week period after the achievement of CR.[13][Level of evidence A3]
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A randomized comparison of IV pegaspargase versus IM native E. coli asparaginase was conducted. Each agent was administered for a 30-week period after the achievement of CR.[13][Level of evidence A3]
Serum asparaginase activity (SAA) levels were significantly higher with IV pegaspargase and exceeded goal therapeutic levels (>0.1 IU/mL) in nearly all patients throughout the 30-week period.
A randomized comparison of IV pegaspargase versus IM native E. coli asparaginase was conducted. Each agent was administered for a 30-week period after the achievement of CR.[13][Level of evidence A3]
There was no significant difference in EFS and OS between the randomized arms.
A randomized comparison of IV pegaspargase versus IM native E. coli asparaginase was conducted. Each agent was administered for a 30-week period after the achievement of CR.[13][Level of evidence A3]
There was no difference in rates of asparaginase-related toxicities, including hypersensitivity, pancreatitis, and thromboembolic complications.
A randomized comparison of IV pegaspargase versus IM native E. coli asparaginase was conducted. Each agent was administered for a 30-week period after the achievement of CR.[13][Level of evidence A3]
Similar outcome and similar rates of asparaginase-related toxicities were observed for both groups of patients.
A randomized comparison of IV pegaspargase versus IM native E. coli asparaginase was conducted. Each agent was administered for a 30-week period after the achievement of CR.[13][Level of evidence A3]
IV pegaspargase was associated with less treatment-related anxiety, as assessed by patient and parent surveys.
Another randomized trial of patients with standard-risk ALL assigned patients to receive either pegaspargase or native E. coli asparaginase during induction and in each of two delayed intensification courses.[15]
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Another randomized trial of patients with standard-risk ALL assigned patients to receive either pegaspargase or native E. coli asparaginase during induction and in each of two delayed intensification courses.[15]
A single dose of pegaspargase given in conjunction with vincristine and prednisone during induction therapy appeared to have similar activity and toxicity as nine doses of IM E. coli L-asparaginase (3 times a week for 3 weeks).[15]
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Another randomized trial of patients with standard-risk ALL assigned patients to receive either pegaspargase or native E. coli asparaginase during induction and in each of two delayed intensification courses.[15]
The use of pegaspargase was associated with more rapid blast clearance and a lower incidence of neutralizing antibodies.
Patients with an allergic reaction to pegaspargase are typically switched to Erwinia L-asparaginase. A COG analysis investigated the deleterious effect on disease-free survival (DFS) of early discontinuation of treatment with pegaspargase in patients with high-risk B-ALL. The study found that the adverse effect on outcome could be reversed with the use of Erwinia L-asparaginase to complete the planned course of asparaginase therapy.[20][Level of evidence C2] Measurement of SAA levels after a mild or questionable reaction to pegaspargase may help to differentiate patients for whom the switch to Erwinia is indicated (because of inadequate SAA) versus those for whom a change in preparation may not be necessary.[21,22]
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Evidence (adverse prognostic impact of early discontinuation of pegaspargase or silent inactivation of asparaginase):
Several studies have identified a subset of patients who experience silent inactivation of asparaginase, which is defined as the absence of therapeutic SAA levels without overt allergy.[23,24] Determination of the optimal frequency of pharmacokinetic monitoring for pegaspargase-treated patients, and whether such screening impacts outcome, awaits further investigation.
Several studies have identified a subset of patients who experience silent inactivation of asparaginase, which is defined as the absence of therapeutic SAA levels without overt allergy.[23,24] Determination of the optimal frequency of pharmacokinetic monitoring for pegaspargase-treated patients, and whether such screening impacts outcome, awaits further investigation.
In a trial conducted by the Dana-Farber Cancer Institute (DFCI) Consortium, 12% of patients who were initially treated with native E.coli L-asparaginase demonstrated silent inactivation. These patients had a superior EFS if their asparaginase preparation was changed.[24]
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Several studies have identified a subset of patients who experience silent inactivation of asparaginase, which is defined as the absence of therapeutic SAA levels without overt allergy.[23,24] Determination of the optimal frequency of pharmacokinetic monitoring for pegaspargase-treated patients, and whether such screening impacts outcome, awaits further investigation.
Patients who were treated with pegaspargase appear to have lower levels of silent inactivation (<10%).[13,23,25]
A report from the COG included 8,196 patients with newly diagnosed B-ALL who were enrolled between 2004 to 2011.[20][Level of evidence C2]
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A report from the COG included 8,196 patients with newly diagnosed B-ALL who were enrolled between 2004 to 2011.[20][Level of evidence C2]
The cumulative incidence of pegaspargase discontinuation (because of toxicity) was 12.2% in NCI standard-risk patients and 25.4% in NCI high-risk patients.
A report from the COG included 8,196 patients with newly diagnosed B-ALL who were enrolled between 2004 to 2011.[20][Level of evidence C2]
In multivariable analysis, NCI high-risk patients who discontinued pegaspargase early had inferior DFS (hazard ratio [HR], 1.5; P = .002) than did those who received all prescribed doses. For NCI standard-risk patients, there was no impact of pegaspargase discontinuation on DFS, except in patients with slow-early response who received intensified postinduction therapy (HR, 1.7; P = .03).
A report from the COG included 8,196 patients with newly diagnosed B-ALL who were enrolled between 2004 to 2011.[20][Level of evidence C2]
NCI high-risk patients who discontinued pegaspargase but then switched to Erwinia asparaginase and received all subsequent intended doses, did not have an increased risk of relapse (HR, 1.1; P = .69).
An analysis of 1,115 non–high-risk ALL patients from the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol reported the following:[25]
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An analysis of 1,115 non–high-risk ALL patients from the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol reported the following:[25]
255 patients received a truncated asparaginase course because of toxicity, and 46 patients had evidence of silent inactivation on therapeutic drug monitoring.
An analysis of 1,115 non–high-risk ALL patients from the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol reported the following:[25]
The 7-year cumulative incidence of relapse was 11.1% in the 301 patients who received a truncated asparaginase course, compared with 6.7% in the remaining 814 patients who received the planned courses (HR, 1.73; P = .03).
An analysis of 1,115 non–high-risk ALL patients from the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol reported the following:[25]
In a Cox model, suboptimal asparaginase treatment (because of either truncated pegaspargase or silent inactivation) was significantly associated with a higher relapse risk (HR, 1.69; P = 0.03).
In an attempt to decrease hypersensitivity reactions to pegaspargase, the Dutch Childhood Oncology Group-ALL11 protocol randomly assigned patients to receive either continuous or noncontinuous dosing after induction therapy. The occurrence of inactivating hypersensitivity reactions was seven times lower and antibody levels were significantly lower in the continuous-dosing arm. There was no difference in total number of asparaginase toxicities or the 5-year incidences of relapse, death, or disease-free survival between the treatment arms.[26]
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Publication references
Read the original reference and check its publication notices.
- PubMed 11877270 · Original source
- PubMed 16434367 · Original source
- PubMed 20007809 · Original source
- PubMed 23358966 · Original source
- PubMed 24449211 · Original source
- PubMed 25393506 · Original source
- PubMed 26549586 · Original source
- PubMed 26928249 · Original source
- PubMed 28660740 · Original source
- PubMed 30626253 · Original source
- PubMed 31657981 · Original source
- PubMed 31922920 · Original source
- PubMed 32275469 · Original source
- PubMed 33150360 · Original source
- PubMed 38306592 · Original source
- PubMed 8355045 · Original source
Preserved source evidence · Not medical advice