Incidence of Allergic Reactions to Pegaspargase (PEG) Administered Intramuscularly Versus Intravenously (IM vs. IV) in Children and Young Adults with High Risk B-Lymphoblastic Leukemia (HR B-ALL): Results of Children's Oncology Group (COG) Studies AALL0232/AALL1131

Abstract

Abstract Introduction: Asparaginase is a vital component of multi-agent chemotherapy for patients with HR B-ALL, but rates of allergic reactions following administration of PEG range from 3-24%. Similar or increased rates of allergic reactions have been reported following IV vs. IM PEG when administered on varying chemotherapy backbones. The COG trials recently changed from IM to IV administration of PEG. We report the rate of allergic reactions/anaphylaxis (Grade 3-4) following IM vs. IV PEG on sequential trials for newly diagnosed patients with HR B-ALL. Methods: Patients 1-30 years of age with newly diagnosed HR B-ALL were eligible for the sequential COG studies, AALL0232 and AALL1131. We limited this analysis to non-Down Syndrome patients who received highly similar chemotherapy regimens prior to maintenance therapy, including a 4-drug Induction with 14 days of dexamethasone or 28 days of prednisone, the COG augmented Berlin-Frankfurt-Munster (BFM) Consolidation, High Dose Methotrexate during Interim Maintenance, and Delayed Intensification (DI). Patients received a total of 5 doses of PEG (2,500 units/m2/dose) administered IM (AALL0232) or IV (AALL1131) during these phases of therapy: Induction (n=1), Consolidation (n=2), DI (n=2). Chi square analysis of the rates of Grade 3-4 allergic reactions/anaphylaxis (Common Terminology Criteria for Adverse Events v4.0) following IM vs. IV PEG was performed. Results: Grade 3-4 allergic reactions/anaphylaxis rates in patients receiving IM vs. IV PEG (Table) were 0.54% vs. 0.22% during Induction (p=0.10), 14.4% vs. 12.64% during Consolidation (p=0.18), and 2.1% vs. 0.97% during DI (p=0.07). Conclusion: Rates of Grade 3-4 allergic reactions/anaphylaxis were similar following IM vs. IV administration of PEG in patients with newly diagnosed HR B-ALL when treated on sequential COG studies, further establishing the safety of delivering IV PEG. Table 1. Allergic Reactions Following IM vs IV PEG Allergic reaction/Anaphylaxis (Grade 3-4) AALL0232(IM PEG) AALL1131(IV PEG) p-value(Chi square test) Induction 15/2771 (0.54%) 4/1797 (0.22%) 0.10 Consolidation 342/2369 (14.4%) 114/902 (12.64%) 0.18 DI 22/1060 (2.1%) 7/715 (0.97%) 0.07 Disclosures Hunger: Spectrum Pharmaceuticals: Consultancy; Jazz Pharmaceuticals: Consultancy; Sigma Tau: Consultancy; Merck: Equity Ownership.