Phase 1b/2 study of blinatumomab in Japanese adults with relapsed/refractory acute lymphoblastic leukemia.

Autor: Kiyoi H; Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Morris JD; Amgen Inc., Thousand Oaks, California, USA., Oh I; Jichi Medical University, Tochigi-ken, Japan., Maeda Y; Okayama University Hospital, Okayama, Japan., Minami H; Medical Oncology/Hematology, Kobe University Graduate School of Medicine and Hospital, Kobe, Japan., Miyamoto T; Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan., Sakura T; Leukemia Research Center, Saiseikai Maebashi Hospital, Maebashi, Japan., Iida H; National Hospital Organization Nagoya Medical Center, Nagoya, Japan., Tuglus CA; Amgen Inc., Thousand Oaks, California, USA., Chen Y; Amgen Inc., Thousand Oaks, California, USA., Dos Santos C; Amgen Inc., South San Francisco, California, USA., Kalabus J; Amgen Inc., South San Francisco, California, USA., Anderson A; Amgen Inc., Thousand Oaks, California, USA., Hata T; Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan., Nakashima Y; Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan., Kobayashi Y; National Cancer Center Hospital, Tokyo, Japan.; International University of Health and Welfare, Mita Hospital, Tokyo, Japan.
Jazyk: angličtina
Zdroj: Cancer science [Cancer Sci] 2020 Apr; Vol. 111 (4), pp. 1314-1323. Date of Electronic Publication: 2020 Feb 11.
DOI: 10.1111/cas.14322
Abstrakt: Adult patients with relapsed/refractory (R/R) B-precursor acute lymphoblastic leukemia (ALL) have a poor prognosis. Blinatumomab is a bispecific T-cell engager (BiTE) immuno-oncology therapy with dual specificity for CD19 and CD3 that redirects patients' CD3-positive cytotoxic T cells to lyse malignant and normal B cells. We conducted an open-label, phase 1b/2 study to determine the safety, pharmacokinetics, efficacy and recommended dose of blinatumomab in Japanese adults with R/R B-precursor ALL. Patients received 9 μg/day blinatumomab during week 1 and 28 μg/day during weeks 2-4, with a 2-week treatment-free interval (6-week cycle); patients received 28 μg/day blinatumomab in subsequent cycles. Primary endpoints were the incidence of dose-limiting toxicities (DLT) in phase 1b and complete remission (CR)/CR with partial hematologic recovery (CRh) within the first two cycles in phase 2. A total of 26 patients enrolled and 25 (96%) reported grade ≥3 adverse events (mostly cytopenias). There were no DLT. CR/CRh within two cycles was achieved by 4 of 5 patients (80%) in phase 1b and 8 of 21 patients (38%) in phase 2. Among patients with evaluable minimal residual disease, 4 (100%) in phase 1b and 3 (38%) in phase 2 had a complete MRD response. Median RFS for 8 patients who achieved CR/CRh in phase 2 was 5 (95% CI: 3.5-6.4) months; median OS was not estimable. There were no significant associations between maximum cytokine levels or percentage of specific cell types during cycle 1 and response. Consistent with global studies, blinatumomab appeared to be safe and efficacious in Japanese adults with R/R ALL.
(© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
Databáze: MEDLINE
Externí odkaz: