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

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 malign...

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Autores principales: Kiyoi, Hitoshi, Morris, Joan D., Oh, Iekuni, Maeda, Yoshinobu, Minami, Hironobu, Miyamoto, Toshihiro, Sakura, Toru, Iida, Hiroatsu, Tuglus, Catherine A., Chen, Yuqi, Dos Santos, Cedric, Kalabus, James, Anderson, Abraham, Hata, Tomoko, Nakashima, Yasuhiro, Kobayashi, Yukio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156857/
https://www.ncbi.nlm.nih.gov/pubmed/31971321
http://dx.doi.org/10.1111/cas.14322
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author Kiyoi, Hitoshi
Morris, Joan D.
Oh, Iekuni
Maeda, Yoshinobu
Minami, Hironobu
Miyamoto, Toshihiro
Sakura, Toru
Iida, Hiroatsu
Tuglus, Catherine A.
Chen, Yuqi
Dos Santos, Cedric
Kalabus, James
Anderson, Abraham
Hata, Tomoko
Nakashima, Yasuhiro
Kobayashi, Yukio
author_facet Kiyoi, Hitoshi
Morris, Joan D.
Oh, Iekuni
Maeda, Yoshinobu
Minami, Hironobu
Miyamoto, Toshihiro
Sakura, Toru
Iida, Hiroatsu
Tuglus, Catherine A.
Chen, Yuqi
Dos Santos, Cedric
Kalabus, James
Anderson, Abraham
Hata, Tomoko
Nakashima, Yasuhiro
Kobayashi, Yukio
author_sort Kiyoi, Hitoshi
collection PubMed
description 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.
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spelling pubmed-71568572020-04-20 Phase 1b/2 study of blinatumomab in Japanese adults with relapsed/refractory acute lymphoblastic leukemia Kiyoi, Hitoshi Morris, Joan D. Oh, Iekuni Maeda, Yoshinobu Minami, Hironobu Miyamoto, Toshihiro Sakura, Toru Iida, Hiroatsu Tuglus, Catherine A. Chen, Yuqi Dos Santos, Cedric Kalabus, James Anderson, Abraham Hata, Tomoko Nakashima, Yasuhiro Kobayashi, Yukio Cancer Sci Original Articles 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. John Wiley and Sons Inc. 2020-02-11 2020-04 /pmc/articles/PMC7156857/ /pubmed/31971321 http://dx.doi.org/10.1111/cas.14322 Text en © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Kiyoi, Hitoshi
Morris, Joan D.
Oh, Iekuni
Maeda, Yoshinobu
Minami, Hironobu
Miyamoto, Toshihiro
Sakura, Toru
Iida, Hiroatsu
Tuglus, Catherine A.
Chen, Yuqi
Dos Santos, Cedric
Kalabus, James
Anderson, Abraham
Hata, Tomoko
Nakashima, Yasuhiro
Kobayashi, Yukio
Phase 1b/2 study of blinatumomab in Japanese adults with relapsed/refractory acute lymphoblastic leukemia
title Phase 1b/2 study of blinatumomab in Japanese adults with relapsed/refractory acute lymphoblastic leukemia
title_full Phase 1b/2 study of blinatumomab in Japanese adults with relapsed/refractory acute lymphoblastic leukemia
title_fullStr Phase 1b/2 study of blinatumomab in Japanese adults with relapsed/refractory acute lymphoblastic leukemia
title_full_unstemmed Phase 1b/2 study of blinatumomab in Japanese adults with relapsed/refractory acute lymphoblastic leukemia
title_short Phase 1b/2 study of blinatumomab in Japanese adults with relapsed/refractory acute lymphoblastic leukemia
title_sort phase 1b/2 study of blinatumomab in japanese adults with relapsed/refractory acute lymphoblastic leukemia
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156857/
https://www.ncbi.nlm.nih.gov/pubmed/31971321
http://dx.doi.org/10.1111/cas.14322
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