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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3756-3762
Number of pages7
JournalJournal of Clinical Oncology
Volume26
Issue number22
DOIs
StatePublished - 2008
Externally publishedYes

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Bone Marrow
Recurrence
Residual Neoplasm
Drug Therapy
Antibodies, Monoclonal, Humanized
Feasibility Studies
epratuzumab
Serum
Flow Cytometry
Seizures
Therapeutics
Pharmaceutical Preparations
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Chemoimmunotherapy reinduction with epratuzumab in children with acute lymphoblastic leukemia in marrow relapse : A children's oncology group pilot study. / Raetz, Elizabeth A.; Cairo, Mitchell S.; Borowitz, Michael J; Blaney, Susan M.; Krailo, Mark D.; Leil, Tarek A.; Reid, Joel M.; Goldenberg, David M.; Wegener, William A.; Carroll, William L.; Adamson, Peter C.

In: Journal of Clinical Oncology, Vol. 26, No. 22, 2008, p. 3756-3762.

Research output: Contribution to journalArticle

Raetz, EA, Cairo, MS, Borowitz, MJ, Blaney, SM, Krailo, MD, Leil, TA, Reid, JM, Goldenberg, DM, Wegener, WA, Carroll, WL & Adamson, PC 2008, 'Chemoimmunotherapy reinduction with epratuzumab in children with acute lymphoblastic leukemia in marrow relapse: A children's oncology group pilot study', Journal of Clinical Oncology, vol. 26, no. 22, pp. 3756-3762. https://doi.org/10.1200/JCO.2007.15.3528
Raetz, Elizabeth A. ; Cairo, Mitchell S. ; Borowitz, Michael J ; Blaney, Susan M. ; Krailo, Mark D. ; Leil, Tarek A. ; Reid, Joel M. ; Goldenberg, David M. ; Wegener, William A. ; Carroll, William L. ; Adamson, Peter C. / Chemoimmunotherapy reinduction with epratuzumab in children with acute lymphoblastic leukemia in marrow relapse : A children's oncology group pilot study. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 22. pp. 3756-3762.
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abstract = "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.",
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T1 - Chemoimmunotherapy reinduction with epratuzumab in children with acute lymphoblastic leukemia in marrow relapse

T2 - A children's oncology group pilot study

AU - Raetz, Elizabeth A.

AU - Cairo, Mitchell S.

AU - Borowitz, Michael J

AU - Blaney, Susan M.

AU - Krailo, Mark D.

AU - Leil, Tarek A.

AU - Reid, Joel M.

AU - Goldenberg, David M.

AU - Wegener, William A.

AU - Carroll, William L.

AU - Adamson, Peter C.

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

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