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Association of Antibodies With Pegaspargase Allergic Reactions and Failure of Rechallenge in Pediatric ALL

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Key Points

  • Of the 81 patients experiencing PEG-ASP allergic reactions, 66 (81.5%) had at least one sample that was positive for anti–PEG-ASP.
  • Failure of rechallenge was associated with positive anti–PEG-ASP status.

In a study reported in the Journal of Clinical Oncology, Liu et al determined the frequency of allergic reactions and consequences of development of antibodies to pegaspargase (PEG-ASP) among pediatric patients with newly diagnosed acute lymphoblastic leukemia (ALL).   

As noted by the investigators, PEG-ASP has largely replaced native Escherichia coli asparaginase (L-ASP) in treatment of ALL due to its longer half-life and lower immunogenicity; however, risk factors for allergic reactions to PEG-ASP remain unclear.

Study Details

PEG-ASP was administered to 598 patients in St Jude’s Total XVI study. Frequency of allergic reactions was compared with that among 410 patients receiving native L-ASP in the Total XV study. Serum samples (n = 5,369) from patients in the XVI study were analyzed for anti–PEG-ASP immunoglobulin G. Positive samples were tested for anti–polyethylene glycol (PEG) and anti–L-ASP antibodies.

Allergic Reactions and Antibody Positivity

Grade 2 to 4 allergic reactions occurred in 81 (13.5%) of 598 patients receiving PEG-ASP in the XVI study vs 169 (41.2%) of 410 patients receiving L-ASP in the XV study (P = 1.43 x10-23). Overall, 11.5% of samples from the XVI population tested positive for anti–PEG-ASP antibody; of the positive samples, 15.5% were positive for both anti-PEG and anti–L-ASP, 80.1% for anti-PEG only, and 1.5% for anti–L-ASP only. Of the 81 patients experiencing PEG-ASP allergic reactions, 66 (81.5%) had at least one sample that was positive for anti–PEG-ASP. Of 517 patients without reactions, 410 (79.3%) never had a positive sample.

Factors Associated With Allergic Reactions

In multivariate analysis, more intrathecal therapy doses were associated with reduced risk of allergic reactions (for 1–3 vs 4–7 doses, 80% vs 92% with no reaction, P = 2.4 x 10-5).

Among 25 patients with allergic reactions rechallenged with PEG-ASP, 16 tolerated rechallenge and 9 experienced failure and had another reaction. In multivariate analysis, failure of rechallenge was associated with anti–PEG-ASP-positive status (P = .027) and occurrence of angioedema with the first allergic reaction (P = .01).

The investigators concluded: “Less intrathecal therapy was the only independent clinical risk factor for reactions to PEG-ASP. PEG, and not L-ASP, is the major antigen that causes allergic reactions. Anti–PEG-ASP has utility in predicting and confirming clinical reactions to PEG-ASP, as well as in identifying patients who are most likely to experience failure with rechallenge.”

Mary V. Relling, PharmD, of the Department of Pharmaceutical Sciences, St Jude Children’s Research Hospital, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by National Institutes of Health grants, Sigma Tau, Baxalta, Shire, and American Lebanese Syrian Associated Charities. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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