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Chemoimmunotherapy Reinduction With Epratuzumab in Children With Acute Lymphoblastic Leukemia in Marrow Relapse: A Children's Oncology Group Pilot Study

Elizabeth A. Raetz, Mitchell S. Cairo, Michael J. Borowitz, Susan M. Blaney, Mark D. Krailo, Tarek A. Leil, Joel M. Reid, David M. Goldenberg, William A. Wegener, William L. Carroll, Peter C. Adamson

From the Department of Pediatrics, New York University; Department of Pediatrics, Columbia University, New York, NY; Department of Pathology, Johns Hopkins, Baltimore, MD; Department of Pediatrics, Baylor College of Medicine, Houston, TX; Children's Oncology Group, Arcadia, CA; Department of Oncology, Mayo Clinic, Rochester, MN; Immunomedics, Inc, Morris Plains, NJ; and Children's Hospital of Philadelphia, Philadelphia, PA

Corresponding author: Elizabeth A. Raetz, MD, New York University School of Medicine, Hassenfeld Children's Center for Cancer and Blood Disorders, 160 East 32nd St, New York, NY 10016; e-mail: elizabeth.raetz{at}nyumc.org

Purpose To determine the tolerability and serum concentration of epratuzumab, a humanized monoclonal antibody targeting CD22, administered alone and in combination with reinduction chemotherapy in children with relapsed acute lymphoblastic leukemia (ALL), and to preliminarily assess tumor targeting and efficacy.

Patients and Methods Therapy consisted of a single-agent phase (epratuzumab 360 mg/m²/dose intravenously twice weekly x four doses), followed by four weekly doses of epratuzumab in combination with standard reinduction chemotherapy. Morphologic and minimal residual disease (MRD) responses were determined at the end of this 6-week period. Serum concentrations of epratuzumab were determined before and 30 minutes after infusions, and CD22 targeting efficiency was determined by quantifying changes in CD22 expression after epratuzumab administration.

Results Fifteen patients (12 fully assessable for toxicity) with first or later CD22-positive ALL marrow relapse enrolled on the feasibility portion of this study from December 2005 to June 2006. Two dose-limiting toxicities occurred: one grade 4 seizure of unclear etiology and one asymptomatic grade 3 ALT elevation. In all but one patient, surface CD22 was not detected by flow cytometry on peripheral blood leukemic blasts within 24 hours of drug administration, indicating effective targeting of leukemic cells by epratuzumab. Nine patients achieved a complete remission after chemoimmunotherapy, seven of whom were MRD negative.

Conclusion Treatment with epratuzumab plus standard reinduction chemotherapy is feasible and acceptably tolerated in children with relapsed CD22-positive ALL. CD22 targeting was efficient, and the majority of patients achieved favorable early responses.

Supported in part by Children's Oncology Group Grant No. U10 CA98543 from the National Cancer Institute.

Presented in part at 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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