Bortezomib-containing therapy in Japanese children with relapsed acute lymphoblastic leukemia
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Outcomes of children treated for relapsed acute lymphoblastic leukemia (ALL) remain poor. Bortezomib (BZM), a proteasome inhibitor, has shown promising activity against lymphoid malignancies. We conducted a phase I study to evaluate the safety and tolerability of multidrug chemotherapy including BZM in Japanese children with relapsed ALL. Three of five children with relapsed ALL enrolled in the study between November 2014 and April 2016 were evaluated. BZM (1.3 mg/m2) was administered on days 8, 11, 15, and 18 of multidrug induction chemotherapy. Pharmacokinetic studies were performed. Age at study entry was 5, 7, and 7 years old, respectively. Two patients had hyperdiploid B-precursor ALL, and one had T cell ALL. Although all patients experienced grade 3–4 hematologic toxicity and grade 3 elevation of aminotransferases, no dose-limiting toxicities were observed. The maximum tolerated dose was defined as 1.3 mg/m2. Peripheral neuropathy and respiratory complications were not observed. Complete remission was achieved in all three patients. The mean maximum plasma concentration and area under the concentration–time curve was 74.0 ng/mL and 73.9 ng h/mL, respectively. Thus, adding BZM to 5-drug induction chemotherapy appears safe and well-tolerated in Japanese children with relapsed ALL.
KeywordsBortezomib Combination chemotherapy Acute lymphoblastic leukemia Relapse Children
This trial was supported by AMED under Grant number JP17ck0106110. We thank all the patients, families, and investigators who participated in this trial.
DH collected samples and data, analyzed data and wrote the manuscript; YY, SK, and TD collected samples and data and analyzed data; NM, JH, AtK, and KH analyzed data and gave conceptual advice; AkK performed the statistical analysis and wrote the manuscript. TK performed pharmacokinetic analyses; YIY performed minimal residual disease analyses; AMS performed data management and monitoring during this trial; AM analyzed data, gave conceptual advice, and wrote the manuscript; CO contributed to the conception and design of this study. All authors have read and approved the final version of the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
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