Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 25, No 18S (June 20 Supplement), 2007: 9513
© 2007 American Society of Clinical Oncology

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Abstract

Chemoimmunotherapy reinduction with epratuzumab in children with ALL with marrow relapse: A Children's Oncology Group (COG) pilot study (ADVL04P2)

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

9513

Background: CD22, a 135kd protein restricted to B-cells, is expressed in > 90% of childhood B-precursor acute lymphoblastic leukemia (ALL). We conducted a feasibility/phase 2 study of epratuzumab, a humanized monoclonal antibody against CD22, with reinduction chemotherapy in children with relapsed CD22+ ALL. Methods: The feasibility portion (n=12) of the study is reported here. Patients with first or later ALL marrow relapse at any time following diagnosis, ± extramedullary disease, with = 25% blasts expressing CD22 and a presenting white blood cell count (WBC) of = 50,000/µl, were eligible. Therapy consisted of a 14-day single agent phase (epratuzumab 360 mg/m² /dose IV twice weekly x 4 doses), followed by 4 weekly doses of epratuzumab in combination with standard reinduction chemotherapy (vincristine, prednisone, PEG-asparaginase, doxorubicin). Remission induction rates and minimal residual disease (MRD) by flow cytometry were determined at the end of this 6-week period. PK studies were performed by ELISA based immunoassay (prior + 30 minutes after infusions). Results: 12 evaluable patients, median age 10 years (range 3 - 18), were accrued. 9 pts were in 1st (n=5 early; n=4 late), and 3 pts in 2nd or later marrow relapse. The mean (±SD) trough epratuzumab concentration increased from 69±23 to 232±74 µg/ml during the initial 14 days. Surface CD22 was not detected by flow cytometry on peripheral blood leukemic blasts within 24 hours of drug administration in all but one patient, indicating effective targeting of leukemic cells by epratuzumab. The most frequent toxicities were grade 1–2 infusion reactions (n=9). Two dose limiting toxicities occurred: one patient had a Grade 4 seizure of unclear etiology and one patient had asymptomatic Grade 3 ALT elevation. 9 patients achieved a complete remission following chemoimmunotherapy, of whom 7 were MRD-negative. Conclusions: Treatment with epratuzumab plus standard reinduction chemotherapy is feasible and well tolerated in children with relapsed ALL, producing favorable early responses in the majority of patients. The phase II portion of the study is ongoing.

Author Disclosure

Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Expert Testimony Other Remuneration Immunomedics Immunomedics Immunomedics

Abstract presentation from the 2007 ASCO Annual Meeting