Bortezomib reinduction chemotherapy in high-risk ALL in first relapse: a report from the Children's Oncology Group

Terzah M. Horton, James A. Whitlock, Xiaomin Lu, Maureen M. O'Brien, Michael J Borowitz, Meenakshi Devidas, Elizabeth A. Raetz, Patrick A Brown, William L. Carroll, Stephen P. Hunger

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Abstract

While survival in paediatric acute lymphoblastic leukaemia (ALL) is excellent, survival following relapse is poor. Previous studies suggest proteasome inhibition with chemotherapy improves relapse ALL response rates. This phase 2 Children's Oncology Group study tested the hypothesis that adding the proteasome inhibitor bortezomib to chemotherapy increases complete response rates (CR2). Evaluable patients (n = 135, 103 B-ALL, 22 T-ALL, 10 T-lymphoblastic lymphoma) were treated with reinduction chemotherapy plus bortezomib. Overall CR2 rates were 68 ± 5% for precursor B-ALL patients (<21 years of age), 63 ± 7% for very early relapse (<18 months from diagnosis) and 72 ± 6% for early relapse (18–36 months from diagnosis). Relapsed T-ALL patients had an encouraging CR2 rate of 68 ± 10%. End of induction minimal residual disease (MRD) significantly predicted survival. MRD negative (MRDneg; MRD <0·01%) rates increased from 29% (post-cycle 1) to 64% following cycle 3. Very early relapse, end-of-induction MRDneg precursor B-ALL patients had 70 ± 14% 3-year event-free (EFS) and overall survival (OS) rates, vs. 3-year EFS/OS of 0–3% (P = 0·0001) for MRDpos (MRD ≥0·01) patients. Early relapse patients had similar outcomes (MRDneg 3-year EFS/OS 58–65% vs. MRDpos 10–19%, EFS P = 0·0014). These data suggest that adding bortezomib to chemotherapy in certain ALL subgroups, such as T-cell ALL, is worthy of further investigation. This study is registered at http://www.clinical.trials.gov as NCT00873093.

Original languageEnglish (US)
JournalBritish journal of haematology
DOIs
StatePublished - Jan 1 2019

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Keywords

  • acute lymphoblastic leukaemia
  • acute lymphocytic leukaemia
  • minimal residual disease
  • paediatric leukaemia
  • proteasome inhibition

ASJC Scopus subject areas

  • Hematology

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