Treatment outcomes for children with relapsed and refractory acute lymphoblastic leukemia (R/R-ALL) remain poor, and the optimal induction therapy has not been determined. Bortezomib is a proteasome inhibitor that acts synergistically and additively with standard chemotherapy for ALL. We evaluated the efficacy and safety of combination chemotherapy with bortezomib in children with R/R-ALL. This single-arm, multicenter, phase 2 study was conducted in Japan between 2016 and 2020. Eligible patients were divided into two cohorts: a high-risk first-relapse cohort of untreated patients with high-risk first-relapsed ALL and an expansion cohort of patients with refractory ALL, including multiple relapses, relapse after allogeneic hematopoietic cell transplantation, and induction failure. All patients received a single course of chemotherapy as induction therapy. Sixteen patients (10 in the high-risk first-relapse cohort, six in the expansion cohort) were evaluable. The overall remission rate after induction therapy was 60% in the high-risk first-relapse cohort and 16.7% in the expansion cohort. All patients had minimal residual disease. Adverse events were acceptable except for interstitial lung disease and hypoxia in a patient in the expansion cohort, but addition of bortezomib to conventional chemotherapy did not produce obvious improvement in children with R/R-ALL.
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The data generated and analyzed in this study are available from the corresponding author on reasonable request.
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The authors thank all patients and parents as well as clinical staff involved in this study. This study was an investigator-initiated clinical trial and supported by a research grant from the Japan Agency for Medical Research and Development (AMED) (Grant number: 20ck0106419h0003). Bortezomib was provided as an investigational agent from Janssen Pharmaceutical K.K. (Tokyo, Japan).
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Miyagawa, N., Goto, H., Ogawa, A. et al. Phase 2 study of combination chemotherapy with bortezomib in children with relapsed and refractory acute lymphoblastic leukemia. Int J Hematol 118, 267–276 (2023). https://doi.org/10.1007/s12185-023-03609-8