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

Pediatr Blood Cancer. 2015 Jul;62(7):1171-5. doi: 10.1002/pbc.25454. Epub 2015 Mar 2.

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.

Keywords: epratuzumab; monoclonal antibody; relapsed ALL.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Immunotherapy*
  • Infant
  • Male
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy*
  • Neoplasm Staging
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Prognosis
  • Remission Induction
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • epratuzumab