Erwinia Asparaginase Safety and Feasibility during Therapy for Acute Lymphoblastic Leukemia in Adult Patients with Pegaspargase Hypersensitivity or Severe Toxicity

• Published in: Blood 2015-12, Vol.126 (23), p.4915-4915
• Main Authors: Horvat, Troy Z, Pecoraro, Joshua J, Daley, Ryan J, Buie, Larry W, Douer, Dan
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V126.23.4915.4915

Introduction: Severe pegaspargase hypersensitivity during first-line therapy for acute lymphoblastic leukemia (ALL) occurs in 1.8-5.9% of patients (Oncaspar [package insert]; Douer D, et al. J Clin Oncol 2014;32:905-911). Erwinia asparaginase is the preferred therapeutic alternative as it retains excellent activity in patients with Escherichia coli asparaginase or pegaspargase antibodies (Willer A, et al. Blood 2011;118:5774-82; Plourde PV, et al. Pediatr Blood Cancer 2014;61:1232-38; Salzer WL, et al. Blood 2013;122:507-14; Zalewska-Szewczyk B, et al. Clin Exp Med 2009;9:113-16). Furthermore, pegaspargase desensitization may not prevent recurrence of severe allergy (Sahiner UM, et al. Pediatr Int 2013;55:531-33). The risk for allergy and other common asparaginase-related adverse effects exists with Erwinia asparaginase, however most data is from pediatric reports. The aim of this study was to assess the safety and feasibility of using Erwinia asparaginase in adult ALL patients with previous pegaspargase hypersensitivity or intolerance. Methods: This is a single-center retrospective analysis of eight adult ALL patients who received Erwinia asparaginase after intolerance to pegaspargase between November 2011 and July 2015. Toxicities were graded using the Common Terminology Criteria for Adverse Events version 4.0. The Memorial Sloan Kettering Investigational Review Board granted an exemption from IRB review. Results: The eight patients received a total of 29 cycles (median 3 cycles each, range 1-6) as part of various pediatric-inspired chemotherapy regimens. Each cycle consisted of Erwinia asparaginase 25,000 units/m2 intramuscularly every 48 hours (either including or excluding weekends). Corticosteroid premedication was given with 52 of 170 total Erwinia asparaginase doses. The median age was 33 years (range 23-72), 7 (87.5%) were males, 75% had B-cell ALL, and 25% had T-cell ALL. Seven patients received Erwinia asparaginase while in first complete remission (CR1) and only one as part of second-line therapy. Patients received a median of 2 prior doses of pegaspargase (range 1-4) before switching to Erwinia asparaginase for either grade 3/4 anaphylaxis (n=6), urticaria/pruritus (n=1), or grade 4 hyperbilirubinemia (n=1). Six patients received all intended cycles, 1 patient was lost to follow up after 1 cycle, and 1 patient was still receiving treatment at the time of analysis. No hypersensitivity reactions occurred and no patient developed arterial or veno