Treatment of children with relapsed and refractory acute lymphoblastic leukemia with mitoxantrone, vincristine, pegaspargase, dexamethasone, and bortezomib

• Published in: Pediatric blood & cancer Vol. 67; no. 3; pp. e28062 - n/a
• Main Authors: August, Keith J., Guest, Erin M., Lewing, Karen, Hays, J. Allyson, Gamis, Alan S.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.03.2020
• Subjects: Acute lymphoblastic leukemia; Adolescent; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asparaginase - administration & dosage; Bortezomib; Bortezomib - administration & dosage; Chemotherapy; Child; Child, Preschool; Children; Dexamethasone; Dexamethasone - administration & dosage; Drug Resistance, Neoplasm - drug effects; Female; Flow cytometry; Follow-Up Studies; Hematology; Humans; Infant; Leukemia; Lymphatic leukemia; Male; Methotrexate; Minimal residual disease; Mitoxantrone; Mitoxantrone - administration & dosage; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Oncology; Patients; Pediatrics; Polyethylene Glycols - administration & dosage; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Prognosis; Proteasome inhibitors; Remission; Salvage Therapy; Stem cells; Steroids; Survival Rate; Targeted cancer therapy; Toxicity; Vincristine; Vincristine - administration & dosage; acute lymphoblastic leukemia; children; chemotherapy
• ISSN: 1545-5009; 1545-5017
• DOI: 10.1002/pbc.28062

Background The treatment of relapsed or refractory acute lymphoblastic leukemia (ALL) in children is challenging and new treatment options are needed. Bortezomib is a proteasome inhibitor with activity in pediatric acute lymphoblastic leukemia. Adding bortezomib to standard reinduction chemotherapy in relapsed and refractory pediatric ALL has produced very good response rates in prior studies. Methods We evaluated bortezomib in combination with reinduction therapy (ALL R3) in 10 children with relapsed or refractory ALL. Bortezomib (1.3 mg/m2/dose) was administered to patients on days 1, 4, 8, and 11. In addition, patients received mitoxantrone, dexamethasone, pegaspargase, vincristine, and intrathecal methotrexate over 4 weeks. Results Of the 10 patients, eight (80%) achieved a complete remission (CR) or complete remission with incomplete recovery (CRi). Of the patients in CR, two had undetectable minimal residual disease by flow cytometry (<0.01%). Five patients were subsequently treated with a stem cell transplant. All eight patients that achieved CR or CRi eventually relapsed. One patient remains alive following treatment with tisagenlecleucel after relapse. Grade 3 or higher infections occurred in four out of 10 patients, and other toxicities commonly associated with bortezomib were not seen. Conclusions In children with relapsed or refractory ALL, the addition of bortezomib to reinduction chemotherapy that includes mitoxantrone produces a complete response in the majority of cases and does not lead to excessive toxicity.