Elizabeth A Raetz1, Mitchell S Cairo2, Michael J Borowitz3, Xiaomin Lu4, Meenakshi Devidas4, Joel M Reid5, David M Goldenberg6, William A Wegener6, Hui Zeng4, James A Whitlock7, Peter C Adamson8, Stephen P Hunger8, William L Carroll9. 1. Department of Pediatrics and Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah. 2. Department of Pediatrics, New York Medical College, New York, New York. 3. Department of Pathology, Johns Hopkins University, Baltimore, Maryland. 4. Department of Biostatistics, Colleges of Medicine, Public Health & Health Professions, University of Florida, Gainesville, Florida. 5. Department of Oncology, Mayo Clinic, Rochester, Minnesota. 6. Immunomedics, Inc., Morris Plains, New Jersey. 7. Department of Pediatrics, University of Toronto and the Hospital for Sick Children, Toronto, Ontario. 8. Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 9. NYU Perlmutter Cancer Center and Department of Pediatrics, NYU Langone Medical Center, New York, New York.
Abstract
BACKGROUND: Given the success of immunotherapeutic approaches in hematologic malignancies, the COG designed a phase I/II study to determine whether the addition of epratuzumab (anti-CD22) to an established chemotherapy platform improves rates of second remission (CR2) in pediatric patients with B-lymphoblastic leukemia (B-ALL) and early bone marrow relapse. PROCEDURE: Therapy consisted of three established blocks of re-induction chemotherapy. Epratuzumab (360 mg/m(2)/dose) was combined with chemotherapy on weekly × 4 (B1) and twice weekly × 4 [eight doses] (B2) schedules during the first re-induction block. Remission rates and minimal residual disease (MRD) status were compared to historical rates observed with the identical chemotherapy platform alone. RESULTS: CR2 was achieved in 65 and 66%, of the evaluable B1 (n = 54) and B2 patients (n = 60), respectively; unchanged from that observed historically without epratuzumab. Rates of MRD negativity (<0.01%) were 31% in B1 (P = 0.4128) and 39% in B2 patients (P = 0.1731), compared to 25% in historical controls. The addition of epratuzumab was well tolerated, with a similar toxicity profile to that observed with the re-induction chemotherapy platform regimen alone. CONCLUSIONS: Epratuzumab was well tolerated in combination with re-induction chemotherapy. While CR2 rates were not improved compared to historical controls treated with chemotherapy alone, there was a non-significant trend towards improvement in MRD response with the addition of epratuzumab (twice weekly for eight doses) to re-induction chemotherapy.
BACKGROUND: Given the success of immunotherapeutic approaches in hematologic malignancies, the COG designed a phase I/II study to determine whether the addition of epratuzumab (anti-CD22) to an established chemotherapy platform improves rates of second remission (CR2) in pediatric patients with B-lymphoblastic leukemia (B-ALL) and early bone marrow relapse. PROCEDURE: Therapy consisted of three established blocks of re-induction chemotherapy. Epratuzumab (360 mg/m(2)/dose) was combined with chemotherapy on weekly × 4 (B1) and twice weekly × 4 [eight doses] (B2) schedules during the first re-induction block. Remission rates and minimal residual disease (MRD) status were compared to historical rates observed with the identical chemotherapy platform alone. RESULTS:CR2 was achieved in 65 and 66%, of the evaluable B1 (n = 54) and B2 patients (n = 60), respectively; unchanged from that observed historically without epratuzumab. Rates of MRD negativity (<0.01%) were 31% in B1 (P = 0.4128) and 39% in B2 patients (P = 0.1731), compared to 25% in historical controls. The addition of epratuzumab was well tolerated, with a similar toxicity profile to that observed with the re-induction chemotherapy platform regimen alone. CONCLUSIONS:Epratuzumab was well tolerated in combination with re-induction chemotherapy. While CR2 rates were not improved compared to historical controls treated with chemotherapy alone, there was a non-significant trend towards improvement in MRD response with the addition of epratuzumab (twice weekly for eight doses) to re-induction chemotherapy.
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