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Dose‐escalation study of tabalumab with bortezomib and dexamethasone in Japanese patients with multiple myeloma
B‐cell activating factor (BAFF) promotes the survival and adhesion of multiple myeloma (MM) cells. Tabalumab (LY2127399) is an anti‐BAFF monoclonal antibody. This phase 1, multicenter, open‐label, nonrandomized, dose‐escalation study evaluated the safety, tolerability, pharmacokinetics, pharmacodyna...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021044/ https://www.ncbi.nlm.nih.gov/pubmed/27350068 http://dx.doi.org/10.1111/cas.13000 |
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author | Iida, Shinsuke Ogiya, Daisuke Abe, Yasunobu Taniwaki, Masafumi Asou, Hiroya Maeda, Kaijiro Uenaka, Kazunori Nagaoka, Soshi Ishiki, Tsuyoshi Conti, Ilaria Tobinai, Kensei |
author_facet | Iida, Shinsuke Ogiya, Daisuke Abe, Yasunobu Taniwaki, Masafumi Asou, Hiroya Maeda, Kaijiro Uenaka, Kazunori Nagaoka, Soshi Ishiki, Tsuyoshi Conti, Ilaria Tobinai, Kensei |
author_sort | Iida, Shinsuke |
collection | PubMed |
description | B‐cell activating factor (BAFF) promotes the survival and adhesion of multiple myeloma (MM) cells. Tabalumab (LY2127399) is an anti‐BAFF monoclonal antibody. This phase 1, multicenter, open‐label, nonrandomized, dose‐escalation study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of tabalumab in combination with bortezomib and dexamethasone in Japanese patients with relapsed or refractory MM (RRMM). Sixteen patients received intravenous i.v. tabalumab 100 mg (Cohort 1, n = 4) or i.v. tabalumab 300 mg (Cohort 2, n = 12) in combination with oral dexamethasone 20 mg/day and i.v. or s.c. bortezomib 1.3 mg/m(2). All patients had treatment‐emergent adverse events (TEAE) possibly related to study treatment; the most common TEAE were thrombocytopenia (81.3%), lymphopenia (43.8%) and increased alanine aminotransferase (43.8%). Two (20.0%) dose‐limiting toxicities were observed, both in Cohort 2 (tabalumab 300 mg), which was below the predefined cutoff for tolerability (<33%). The pharmacokinetics of tabalumab were similar when bortezomib was coadministered i.v. versus s.c. The overall response rate was 56.3%, suggesting that the combined treatment was effective. In conclusion, combined treatment with these three agents was well tolerated in this population of Japanese patients with RRMM. The study was registered at www.clinicaltrials.gov (NCT01556438). |
format | Online Article Text |
id | pubmed-5021044 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-50210442016-09-20 Dose‐escalation study of tabalumab with bortezomib and dexamethasone in Japanese patients with multiple myeloma Iida, Shinsuke Ogiya, Daisuke Abe, Yasunobu Taniwaki, Masafumi Asou, Hiroya Maeda, Kaijiro Uenaka, Kazunori Nagaoka, Soshi Ishiki, Tsuyoshi Conti, Ilaria Tobinai, Kensei Cancer Sci Original Articles B‐cell activating factor (BAFF) promotes the survival and adhesion of multiple myeloma (MM) cells. Tabalumab (LY2127399) is an anti‐BAFF monoclonal antibody. This phase 1, multicenter, open‐label, nonrandomized, dose‐escalation study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of tabalumab in combination with bortezomib and dexamethasone in Japanese patients with relapsed or refractory MM (RRMM). Sixteen patients received intravenous i.v. tabalumab 100 mg (Cohort 1, n = 4) or i.v. tabalumab 300 mg (Cohort 2, n = 12) in combination with oral dexamethasone 20 mg/day and i.v. or s.c. bortezomib 1.3 mg/m(2). All patients had treatment‐emergent adverse events (TEAE) possibly related to study treatment; the most common TEAE were thrombocytopenia (81.3%), lymphopenia (43.8%) and increased alanine aminotransferase (43.8%). Two (20.0%) dose‐limiting toxicities were observed, both in Cohort 2 (tabalumab 300 mg), which was below the predefined cutoff for tolerability (<33%). The pharmacokinetics of tabalumab were similar when bortezomib was coadministered i.v. versus s.c. The overall response rate was 56.3%, suggesting that the combined treatment was effective. In conclusion, combined treatment with these three agents was well tolerated in this population of Japanese patients with RRMM. The study was registered at www.clinicaltrials.gov (NCT01556438). John Wiley and Sons Inc. 2016-09-01 2016-09 /pmc/articles/PMC5021044/ /pubmed/27350068 http://dx.doi.org/10.1111/cas.13000 Text en © 2016 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 Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Iida, Shinsuke Ogiya, Daisuke Abe, Yasunobu Taniwaki, Masafumi Asou, Hiroya Maeda, Kaijiro Uenaka, Kazunori Nagaoka, Soshi Ishiki, Tsuyoshi Conti, Ilaria Tobinai, Kensei Dose‐escalation study of tabalumab with bortezomib and dexamethasone in Japanese patients with multiple myeloma |
title | Dose‐escalation study of tabalumab with bortezomib and dexamethasone in Japanese patients with multiple myeloma |
title_full | Dose‐escalation study of tabalumab with bortezomib and dexamethasone in Japanese patients with multiple myeloma |
title_fullStr | Dose‐escalation study of tabalumab with bortezomib and dexamethasone in Japanese patients with multiple myeloma |
title_full_unstemmed | Dose‐escalation study of tabalumab with bortezomib and dexamethasone in Japanese patients with multiple myeloma |
title_short | Dose‐escalation study of tabalumab with bortezomib and dexamethasone in Japanese patients with multiple myeloma |
title_sort | dose‐escalation study of tabalumab with bortezomib and dexamethasone in japanese patients with multiple myeloma |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021044/ https://www.ncbi.nlm.nih.gov/pubmed/27350068 http://dx.doi.org/10.1111/cas.13000 |
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