Re-induction chemoimmunotherapy with epratuzumab in relapsed acute lymphoblastic leukemia (ALL): Phase II results from Children's Oncology Group (COG) study ADVL04P2.
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.


METHODS
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.
Department of Pediatrics and Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
Elizabeth A
EA
Raetz
Department of Pediatrics, New York Medical College, New York, New York.
Mitchell S
MS
Cairo
Department of Pathology, Johns Hopkins University, Baltimore, Maryland.
Michael J
MJ
Borowitz
Department of Biostatistics, Colleges of Medicine, Public Health & Health Professions, University of Florida, Gainesville, Florida.
Xiaomin
X
Lu
Department of Biostatistics, Colleges of Medicine, Public Health & Health Professions, University of Florida, Gainesville, Florida.
Meenakshi
M
Devidas
Department of Oncology, Mayo Clinic, Rochester, Minnesota.
Joel M
JM
Reid
Immunomedics, Inc., Morris Plains, New Jersey.
David M
DM
Goldenberg
Immunomedics, Inc., Morris Plains, New Jersey.
William A
WA
Wegener
Department of Biostatistics, Colleges of Medicine, Public Health & Health Professions, University of Florida, Gainesville, Florida.
Hui
H
Zeng
Department of Pediatrics, University of Toronto and the Hospital for Sick Children, Toronto, Ontario.
James A
JA
Whitlock
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Peter C
PC
Adamson
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Stephen P
SP
Hunger
NYU Perlmutter Cancer Center and Department of Pediatrics, NYU Langone Medical Center, New York, New York.
William L
WL
Carroll
D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D012074:Remission Induction; D055815:Young Adult
D061067:Antibodies, Monoclonal, Humanized; C448700:epratuzumab
epratuzumab; monoclonal antibody; relapsed ALL