Bortezomib-containing therapy in Japanese children with relapsed acute lymphoblastic leukemia

• Published in: International journal of hematology Vol. 110; no. 5; pp. 627 - 634
• Main Authors: Hasegawa, Daisuke, Yoshimoto, Yuri, Kimura, Shunsuke, Kumamoto, Tadashi, Maeda, Naoko, Hara, Junichi, Kikuta, Atsushi, Kada, Akiko, Kimura, Toshimi, Iijima-Yamashita, Yuka, Saito, Akiko M., Horibe, Keizo, Manabe, Atsushi, Ogawa, Chitose
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.11.2019; Springer Nature B.V
• Subjects: Acute lymphoblastic leukemia; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bortezomib; Bortezomib - administration & dosage; Bortezomib - adverse effects; Chemotherapy; Child; Child, Preschool; Children; Complications; Hematology; Humans; Inhibitor drugs; Japan; Leukemia; Lymphatic leukemia; Lymphocytes; Lymphocytes T; Maximum Tolerated Dose; Medicine; Medicine & Public Health; Oncology; Original Article; Peripheral neuropathy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Proteasome inhibitors; Recurrence; Remission; Salvage Therapy - adverse effects; Salvage Therapy - methods; Targeted cancer therapy; Toxicity; Treatment Outcome; Japan; Relapse; Bortezomib; Children; Acute lymphoblastic leukemia; Combination chemotherapy
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-019-02714-x

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/m 2 ) 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/m 2 . 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.