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Silent NK/T cell reactions to dasatinib during sustained deep molecular response before cessation are associated with longer treatment‐free remission
This study presents the final report of the multicenter, prospective tyrosine kinase inhibitor discontinuation study, D‐STOP, after a 3‐year follow‐up of 54 patients with chronic CML who discontinued dasatinib after a sustained deep molecular response (DMR) for ≥2 years with dasatinib treatment. Est...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419041/ https://www.ncbi.nlm.nih.gov/pubmed/32614159 http://dx.doi.org/10.1111/cas.14518 |
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author | Kumagai, Takashi Nakaseko, Chiaki Nishiwaki, Kaichi Yoshida, Chikashi Ohashi, Kazuteru Takezako, Naoki Takano, Hina Kouzai, Yasuji Murase, Tadashi Matsue, Kosei Morita, Satoshi Sakamoto, Junichi Wakita, Hisashi Sakamaki, Hisashi Inokuchi, Koiti |
author_facet | Kumagai, Takashi Nakaseko, Chiaki Nishiwaki, Kaichi Yoshida, Chikashi Ohashi, Kazuteru Takezako, Naoki Takano, Hina Kouzai, Yasuji Murase, Tadashi Matsue, Kosei Morita, Satoshi Sakamoto, Junichi Wakita, Hisashi Sakamaki, Hisashi Inokuchi, Koiti |
author_sort | Kumagai, Takashi |
collection | PubMed |
description | This study presents the final report of the multicenter, prospective tyrosine kinase inhibitor discontinuation study, D‐STOP, after a 3‐year follow‐up of 54 patients with chronic CML who discontinued dasatinib after a sustained deep molecular response (DMR) for ≥2 years with dasatinib treatment. Estimated treatment‐free remission (TFR) rates at 12 and 36 months were 63.0% [95% confidence interval (CI): 48.7‐74.3] and 59.3% (95% CI: 45.0‐71.0), respectively. CD3(−)CD56(+ )NK, CD16(+)CD56(+ )NK, and CD57(+)CD56(+ )NK large granular lymphocyte (NK‐LGL), CD8(+)CD4(–) cytotoxic T cell, and CD57(+)CD3(+ )T‐LGL cell numbers were relatively elevated throughout the 24‐month consolidation only in failed patients who molecularly relapsed within 12 months. In successful patients, these subsets elevated transiently after 12 months, but returned to basal levels after 24‐month consolidation. Therefore, smaller changes in NK/T, particularly the NK subset throughout consolidation, reflected higher TFR rates. TFR rates of those patients exhibiting elevation in CD3(−)CD56(+ )NK >376 cells/μL, CD16(+)CD56(+ )NK > 241 cells/μL, or CD57(+)CD56(+ )NK‐LGL >242 cells/μL during consolidation compared with others were 26.7% (8.3%‐49.6%) vs 78.3% (55.4%‐90.3%), HR 0.032 (0.0027‐0.38; P = .0064), 31.2% (11.4%‐53.6%) vs 85.0% (60.4%‐94.9%), HR 0.039 (0.0031‐0.48; P = .011), or 36.8% (16.5%‐57.5%) vs 77.3% (53.7%‐89.8%), HR 0.21 (0.065‐0.69; P = .010), respectively. Therefore, silent responses of T/NK subsets to dasatinib throughout consolidation were significant for longer TFR. Elevated NK/T, particularly NK lymphocytes responsive to dasatinib, may be immunologically insufficient to maintain TFR. Their decline, subsequently replaced by altered lymphocyte population with less response to dasatinib during sustained DMR, might be immunologically significant. (D‐STOP, NCT01627132). |
format | Online Article Text |
id | pubmed-7419041 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74190412020-08-12 Silent NK/T cell reactions to dasatinib during sustained deep molecular response before cessation are associated with longer treatment‐free remission Kumagai, Takashi Nakaseko, Chiaki Nishiwaki, Kaichi Yoshida, Chikashi Ohashi, Kazuteru Takezako, Naoki Takano, Hina Kouzai, Yasuji Murase, Tadashi Matsue, Kosei Morita, Satoshi Sakamoto, Junichi Wakita, Hisashi Sakamaki, Hisashi Inokuchi, Koiti Cancer Sci Original Articles This study presents the final report of the multicenter, prospective tyrosine kinase inhibitor discontinuation study, D‐STOP, after a 3‐year follow‐up of 54 patients with chronic CML who discontinued dasatinib after a sustained deep molecular response (DMR) for ≥2 years with dasatinib treatment. Estimated treatment‐free remission (TFR) rates at 12 and 36 months were 63.0% [95% confidence interval (CI): 48.7‐74.3] and 59.3% (95% CI: 45.0‐71.0), respectively. CD3(−)CD56(+ )NK, CD16(+)CD56(+ )NK, and CD57(+)CD56(+ )NK large granular lymphocyte (NK‐LGL), CD8(+)CD4(–) cytotoxic T cell, and CD57(+)CD3(+ )T‐LGL cell numbers were relatively elevated throughout the 24‐month consolidation only in failed patients who molecularly relapsed within 12 months. In successful patients, these subsets elevated transiently after 12 months, but returned to basal levels after 24‐month consolidation. Therefore, smaller changes in NK/T, particularly the NK subset throughout consolidation, reflected higher TFR rates. TFR rates of those patients exhibiting elevation in CD3(−)CD56(+ )NK >376 cells/μL, CD16(+)CD56(+ )NK > 241 cells/μL, or CD57(+)CD56(+ )NK‐LGL >242 cells/μL during consolidation compared with others were 26.7% (8.3%‐49.6%) vs 78.3% (55.4%‐90.3%), HR 0.032 (0.0027‐0.38; P = .0064), 31.2% (11.4%‐53.6%) vs 85.0% (60.4%‐94.9%), HR 0.039 (0.0031‐0.48; P = .011), or 36.8% (16.5%‐57.5%) vs 77.3% (53.7%‐89.8%), HR 0.21 (0.065‐0.69; P = .010), respectively. Therefore, silent responses of T/NK subsets to dasatinib throughout consolidation were significant for longer TFR. Elevated NK/T, particularly NK lymphocytes responsive to dasatinib, may be immunologically insufficient to maintain TFR. Their decline, subsequently replaced by altered lymphocyte population with less response to dasatinib during sustained DMR, might be immunologically significant. (D‐STOP, NCT01627132). John Wiley and Sons Inc. 2020-06-26 2020-08 /pmc/articles/PMC7419041/ /pubmed/32614159 http://dx.doi.org/10.1111/cas.14518 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 Kumagai, Takashi Nakaseko, Chiaki Nishiwaki, Kaichi Yoshida, Chikashi Ohashi, Kazuteru Takezako, Naoki Takano, Hina Kouzai, Yasuji Murase, Tadashi Matsue, Kosei Morita, Satoshi Sakamoto, Junichi Wakita, Hisashi Sakamaki, Hisashi Inokuchi, Koiti Silent NK/T cell reactions to dasatinib during sustained deep molecular response before cessation are associated with longer treatment‐free remission |
title | Silent NK/T cell reactions to dasatinib during sustained deep molecular response before cessation are associated with longer treatment‐free remission |
title_full | Silent NK/T cell reactions to dasatinib during sustained deep molecular response before cessation are associated with longer treatment‐free remission |
title_fullStr | Silent NK/T cell reactions to dasatinib during sustained deep molecular response before cessation are associated with longer treatment‐free remission |
title_full_unstemmed | Silent NK/T cell reactions to dasatinib during sustained deep molecular response before cessation are associated with longer treatment‐free remission |
title_short | Silent NK/T cell reactions to dasatinib during sustained deep molecular response before cessation are associated with longer treatment‐free remission |
title_sort | silent nk/t cell reactions to dasatinib during sustained deep molecular response before cessation are associated with longer treatment‐free remission |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419041/ https://www.ncbi.nlm.nih.gov/pubmed/32614159 http://dx.doi.org/10.1111/cas.14518 |
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