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

Summary 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 tha...

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Vydané v:British journal of haematology Ročník 186; číslo 2; s. 274 - 285
Hlavní autori: Horton, Terzah M., Whitlock, James A., Lu, Xiaomin, O'Brien, Maureen M., Borowitz, Michael J., Devidas, Meenakshi, Raetz, Elizabeth A., Brown, Patrick A., Carroll, William L., Hunger, Stephen P.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: England Blackwell Publishing Ltd 01.07.2019
Predmet:
acute lymphoblastic leukaemia
Acute lymphoblastic leukemia
acute lymphocytic leukaemia
Adolescent
Adult
Bortezomib
Bortezomib - administration & dosage
Bortezomib - adverse effects
Chemotherapy
Child
Child, Preschool
Children
Clinical trials
Diagnosis
Disease-Free Survival
Female
Hematology
Humans
Infant
Leukemia
Lymphoma
Male
Minimal residual disease
Neoplasm, Residual
Oncology
paediatric leukaemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality
proteasome inhibition
Proteasome inhibitors
Recurrence
Survival Rate
Time Factors
proteasome inhibition
acute lymphocytic leukaemia
minimal residual disease
acute lymphoblastic leukaemia
paediatric leukaemia
ISSN:0007-1048, 1365-2141, 1365-2141
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Shrnutí:Summary 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.
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Authorship: Terzah Horton, James Whitlock, Meena Devidas, Xioamin Lu and Stephen Hunger designed and analysed the research study. The clinical trial was conducted by COG; Terzah Horton was the principle investigator for the trial. Data Analysis was conducted by Terzah Horton, Meena Devidas, Xiaomin Lu, Michael Borowitz and Stephen Hunger. The manuscript was written by Terzah Horton and critical revisions were provided by James Whitlock, Xiaomin Lu, Maureen M. O’Brien, Michael Borowitz, Meenakshi Devidas, Elizabeth Raetz, Patrick Brown, William Carroll and Stephen Hunger. Final approval of manuscript was provided by Terzah Horton, James Whitlock, Xiaomin Lu, Maureen M. O’Brien, Michael Borowitz, Meenakshi Devidas, Elizabeth Raetz, Patrick Brown, William Carroll and Stephen Hunger.
ISSN:0007-1048
1365-2141
1365-2141
DOI:10.1111/bjh.15919