Pharmacokinetic and clinical considerations for monitoring asparaginase activity levels during pegaspargase therapy

Benitez, Lydia; Perissinotti, Anthony J.; Santarossa, Maressa; Marini, Bernard L.

doi:10.1002/pbc.25426

Cited by 7 publications

(4 citation statements)

References 8 publications

(13 reference statements)

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“…Additionally, with the vast majority of pediatric ALL patients treated on national clinical trial protocols, data on adverse effects related to PEG‐ASP from large multicenter clinical trials should be collated to determine if increased monitoring, VTE prophylaxis, or dose capping at 3,750 IU should be incorporated into these national protocols. Furthermore, recent data published on the use of asparaginase activity levels for therapeutic drug monitoring and PEG‐ASP dose adjustments suggest that incorporation of asparaginase activity levels into upcoming treatment protocols might be one strategy available for reducing PEG‐ASP dose‐related toxicities in the future …”

Section: Discussionmentioning

confidence: 99%

Adverse effects of pegaspargase in pediatric patients receiving doses greater than 3,750 IU

Lebovic

Pearce

Lacey

et al. 2017

Pediatric Blood & Cancer

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Section: Discussionmentioning

confidence: 99%

Adverse effects of pegaspargase in pediatric patients receiving doses greater than 3,750 IU

Lebovic

Pearce

Lacey

et al. 2017

Pediatric Blood & Cancer

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“…24 Recently, the National Comprehensive Cancer Network clinical practice guidelines and other expert reviews on ASNase hypersensitivity recommended switching of ASNase preparations only in the event of grade ≥ 3, severe or lifethreatening allergic or anaphylactic reactions. 36,[41][42][43] In addition, due to the repeated shortage of Erwinia ASNase various strategies were evaluated in order to avoid or delay the switch to Erwinia ASNase as long as possible. 36,44,45 Thus, PEG-ASNase was either generally administered under premedication or in case of hypersensitivity reactions grade ≤ 2 under premedication at initially reduced infusion rates.…”

Section: Symptoms Of Moderate Hypersensitivity Reactions (Ctcae Gradementioning

confidence: 99%

Pre-existing antibodies against polyethylene glycol reduce asparaginase activities on first administration of pegylated <i>E. coli</i> asparaginase in children with acute lymphocytic leukemia

et al. 2020

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Antibodies against polyethylene glycol (PEG) in healthy subjects raise concerns about the efficacy of pegylated drugs. We evaluated the prevalence of antibodies against PEG among patients with acute lymphoblastic leukemia (ALL) prior to and/or immediately after their first dose of pegylated E.coli asparaginase (PEG-ASNase). Serum samples of 701 children, 673 with primary ALL, 28 with relapsed ALL, and 188 adults with primary ALL were analyzed for anti-PEG IgG and IgM. Measurements in 58 healthy infants served as reference to define cut-points for antibody-positive and -negative samples. Anti-PEG antibodies were detected in ALL patients prior the first PEG-ASNase with a prevalence of 13.9% (anti-PEG IgG) and 29.1% (anti-PEG IgM). After administration of PEG-ASNase the prevalence of anti-PEG antibodies decreased to 4.2% for anti-PEG IgG and to 4.5% for anti-PEG IgM. Pre-existing anti-PEG antibodies did not inhibit PEG-ASNase activity but significantly reduced PEGASNase activity levels in a concentration dependent manner. Although pre-existing anti-PEG antibodies did not boost, pre-existing anti-PEG IgG were significantly associated with firstexposure hypersensitivity reactions (CTCAE grade 2) (p

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“…While the benefits of asparaginase activity monitoring are generally acknowledged, the optimal asparaginase activity level and appropriate use of monitoring in clinical practice remains the subject of debate [28,68,82,83]. There are two primary ways that asparaginase activity monitoring can be utilized in practice: (1) to identify patients with silent inactivation, and (2) to incrementally adjust asparaginase doses in individual patients to achieve 'optimal' asparaginase activity.…”

Section: Recommendations For Asparaginase Activity Monitoringmentioning

confidence: 99%

Asparaginase activity levels and monitoring in patients with acute lymphoblastic leukemia

Salzer

Bostrom²,

Messinger³

et al. 2017

Leukemia & Lymphoma

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Asparaginase is an integral component of multiagent chemotherapy regimens for the treatment of acute lymphoblastic leukemia (ALL). Adequate asparagine depletion is believed to be an important factor in achieving optimal therapeutic outcomes. Measurement of asparaginase activity allows practitioners to evaluate the potential effectiveness of therapy in real time. Asparaginase activity levels can be used to identify patients with silent inactivation and modify therapy in these patients. Patients with silent inactivation to asparaginase who are switched to therapy with an immunologically distinct asparaginase exhibit outcomes similar to patients who never developed silent inactivation. Despite these benefits, there exists no universally agreed-upon guideline for treatment adjustments based on asparaginase activity levels. The goal of this manuscript is to review the clinical evidence linking asparaginase activity levels to outcomes in patients with ALL and to provide an overview of how asparaginase activity levels may be used to guide treatment.

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Pharmacokinetic and clinical considerations for monitoring asparaginase activity levels during pegaspargase therapy

Cited by 7 publications

References 8 publications

Adverse effects of pegaspargase in pediatric patients receiving doses greater than 3,750 IU

Adverse effects of pegaspargase in pediatric patients receiving doses greater than 3,750 IU

Pre-existing antibodies against polyethylene glycol reduce asparaginase activities on first administration of pegylated <i>E. coli</i> asparaginase in children with acute lymphocytic leukemia

Asparaginase activity levels and monitoring in patients with acute lymphoblastic leukemia

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