Pretransplantation Anti-CCR4 Antibody Mogamulizumab Against Adult T-Cell Leukemia/Lymphoma Is Associated With Significantly Increased Risks of Severe and Corticosteroid-Refractory Graft-Versus-Host Disease, Nonrelapse Mortality, and Overall Mortality
Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one important treatment option for patients with aggressive adult T-cell leukemia/lymphoma (ATLL). Mogamulizumab (anti-CCR4 monoclonal antibody; Mog) was recently approved as a treatment for ATLL in Japan. Major concerns exist about t...
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| Veröffentlicht in: | Journal of clinical oncology 2016-10, Vol.34 (28), p.3426-3433 |
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| creator | Fuji, Shigeo Inoue, Yoshitaka Utsunomiya, Atae Moriuchi, Yukiyoshi Uchimaru, Kaoru Choi, Ilseung Otsuka, Eiichi Henzan, Hideho Kato, Koji Tomoyose, Takeaki Yamamoto, Hisashi Kurosawa, Saiko Matsuoka, Ken-Ichi Yamaguchi, Takuhiro Fukuda, Takahiro |
| description | Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one important treatment option for patients with aggressive adult T-cell leukemia/lymphoma (ATLL). Mogamulizumab (anti-CCR4 monoclonal antibody; Mog) was recently approved as a treatment for ATLL in Japan. Major concerns exist about the possible adverse effects of pretransplantation Mog because Mog depletes regulatory T cells for several months. We assessed the impact of pretransplantation Mog on clinical outcomes after allo-HSCT.
We included 996 allo-HSCT recipients age 70 years or younger with aggressive ATLL who were given the diagnosis between 2000 and 2013 and who received intensive chemotherapy by multiple chemotherapeutic drugs as first-line therapy. Before allo-HSCT, 82 patients received Mog with a median interval of 45 days from the last Mog to allo-HSCT.
Pretransplantation Mog was associated with an increased risk of grade 3 to 4 acute graft-versus-host disease (GVHD; relative risk, 1.80; P < .01) and refractoriness to systemic corticosteroid for acute GVHD (relative risk, 2.09; P < .01). One-year cumulative incidence of nonrelapse mortality was significantly higher in patients with pretransplantation Mog compared with those without (43.7% v 25.1%; P < .01). The probability of 1-year overall survival was also significantly inferior in patients with pretransplantation Mog compared with those without (32.3% v 49.4%; P < .01). In particular, use of Mog with intervals < 50 days to allo-HSCT was associated with a dismal clinical outcome.
Pretransplantation Mog was significantly associated with an increased risk of GVHD-related mortality, which supports the relevance of CCR4-expressing Tregs after allo-HSCT in humans. In clinical practice, Mog should be cautiously used for patients with ATLL who are eligible for allo-HSCT. |
| doi_str_mv | 10.1200/JCO.2016.67.8250 |
| format | Article |
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We included 996 allo-HSCT recipients age 70 years or younger with aggressive ATLL who were given the diagnosis between 2000 and 2013 and who received intensive chemotherapy by multiple chemotherapeutic drugs as first-line therapy. Before allo-HSCT, 82 patients received Mog with a median interval of 45 days from the last Mog to allo-HSCT.
Pretransplantation Mog was associated with an increased risk of grade 3 to 4 acute graft-versus-host disease (GVHD; relative risk, 1.80; P < .01) and refractoriness to systemic corticosteroid for acute GVHD (relative risk, 2.09; P < .01). One-year cumulative incidence of nonrelapse mortality was significantly higher in patients with pretransplantation Mog compared with those without (43.7% v 25.1%; P < .01). The probability of 1-year overall survival was also significantly inferior in patients with pretransplantation Mog compared with those without (32.3% v 49.4%; P < .01). In particular, use of Mog with intervals < 50 days to allo-HSCT was associated with a dismal clinical outcome.
Pretransplantation Mog was significantly associated with an increased risk of GVHD-related mortality, which supports the relevance of CCR4-expressing Tregs after allo-HSCT in humans. In clinical practice, Mog should be cautiously used for patients with ATLL who are eligible for allo-HSCT.</description><identifier>ISSN: 0732-183X</identifier><identifier>EISSN: 1527-7755</identifier><identifier>DOI: 10.1200/JCO.2016.67.8250</identifier><identifier>PMID: 27507878</identifier><language>eng</language><publisher>United States</publisher><subject>Acute Disease ; Adrenal Cortex Hormones - therapeutic use ; Adult ; Aged ; Antibodies, Monoclonal, Humanized - adverse effects ; Antibodies, Monoclonal, Humanized - therapeutic use ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Databases, Factual ; Female ; Graft vs Host Disease - chemically induced ; Graft vs Host Disease - drug therapy ; Graft vs Host Disease - etiology ; Graft vs Host Disease - immunology ; Hematopoietic Stem Cell Transplantation - adverse effects ; Hematopoietic Stem Cell Transplantation - methods ; Humans ; Leukemia-Lymphoma, Adult T-Cell - drug therapy ; Leukemia-Lymphoma, Adult T-Cell - mortality ; Leukemia-Lymphoma, Adult T-Cell - therapy ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Transplantation, Homologous ; Young Adult</subject><ispartof>Journal of clinical oncology, 2016-10, Vol.34 (28), p.3426-3433</ispartof><rights>2016 by American Society of Clinical Oncology.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c346t-bcb69e4c252d055684f9e19b3dadbbd101f9722e9e5f36ac9d06c8904ae5ebfc3</citedby><cites>FETCH-LOGICAL-c346t-bcb69e4c252d055684f9e19b3dadbbd101f9722e9e5f36ac9d06c8904ae5ebfc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3729,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27507878$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fuji, Shigeo</creatorcontrib><creatorcontrib>Inoue, Yoshitaka</creatorcontrib><creatorcontrib>Utsunomiya, Atae</creatorcontrib><creatorcontrib>Moriuchi, Yukiyoshi</creatorcontrib><creatorcontrib>Uchimaru, Kaoru</creatorcontrib><creatorcontrib>Choi, Ilseung</creatorcontrib><creatorcontrib>Otsuka, Eiichi</creatorcontrib><creatorcontrib>Henzan, Hideho</creatorcontrib><creatorcontrib>Kato, Koji</creatorcontrib><creatorcontrib>Tomoyose, Takeaki</creatorcontrib><creatorcontrib>Yamamoto, Hisashi</creatorcontrib><creatorcontrib>Kurosawa, Saiko</creatorcontrib><creatorcontrib>Matsuoka, Ken-Ichi</creatorcontrib><creatorcontrib>Yamaguchi, Takuhiro</creatorcontrib><creatorcontrib>Fukuda, Takahiro</creatorcontrib><title>Pretransplantation Anti-CCR4 Antibody Mogamulizumab Against Adult T-Cell Leukemia/Lymphoma Is Associated With Significantly Increased Risks of Severe and Corticosteroid-Refractory Graft-Versus-Host Disease, Nonrelapse Mortality, and Overall Mortality</title><title>Journal of clinical oncology</title><addtitle>J Clin Oncol</addtitle><description>Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one important treatment option for patients with aggressive adult T-cell leukemia/lymphoma (ATLL). Mogamulizumab (anti-CCR4 monoclonal antibody; Mog) was recently approved as a treatment for ATLL in Japan. Major concerns exist about the possible adverse effects of pretransplantation Mog because Mog depletes regulatory T cells for several months. We assessed the impact of pretransplantation Mog on clinical outcomes after allo-HSCT.
We included 996 allo-HSCT recipients age 70 years or younger with aggressive ATLL who were given the diagnosis between 2000 and 2013 and who received intensive chemotherapy by multiple chemotherapeutic drugs as first-line therapy. Before allo-HSCT, 82 patients received Mog with a median interval of 45 days from the last Mog to allo-HSCT.
Pretransplantation Mog was associated with an increased risk of grade 3 to 4 acute graft-versus-host disease (GVHD; relative risk, 1.80; P < .01) and refractoriness to systemic corticosteroid for acute GVHD (relative risk, 2.09; P < .01). One-year cumulative incidence of nonrelapse mortality was significantly higher in patients with pretransplantation Mog compared with those without (43.7% v 25.1%; P < .01). The probability of 1-year overall survival was also significantly inferior in patients with pretransplantation Mog compared with those without (32.3% v 49.4%; P < .01). In particular, use of Mog with intervals < 50 days to allo-HSCT was associated with a dismal clinical outcome.
Pretransplantation Mog was significantly associated with an increased risk of GVHD-related mortality, which supports the relevance of CCR4-expressing Tregs after allo-HSCT in humans. In clinical practice, Mog should be cautiously used for patients with ATLL who are eligible for allo-HSCT.</description><subject>Acute Disease</subject><subject>Adrenal Cortex Hormones - therapeutic use</subject><subject>Adult</subject><subject>Aged</subject><subject>Antibodies, Monoclonal, Humanized - adverse effects</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Databases, Factual</subject><subject>Female</subject><subject>Graft vs Host Disease - chemically induced</subject><subject>Graft vs Host Disease - drug therapy</subject><subject>Graft vs Host Disease - etiology</subject><subject>Graft vs Host Disease - immunology</subject><subject>Hematopoietic Stem Cell Transplantation - adverse effects</subject><subject>Hematopoietic Stem Cell Transplantation - methods</subject><subject>Humans</subject><subject>Leukemia-Lymphoma, Adult T-Cell - drug therapy</subject><subject>Leukemia-Lymphoma, Adult T-Cell - mortality</subject><subject>Leukemia-Lymphoma, Adult T-Cell - therapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Retrospective Studies</subject><subject>Survival Rate</subject><subject>Transplantation, Homologous</subject><subject>Young Adult</subject><issn>0732-183X</issn><issn>1527-7755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kU1v1DAQhiMEokvhzgn5yKHZ2k6cj2MUoF20sGhbPm7RxJ5sTZM42A5S-Omc8LalJ4_sdx6P5omi14yuGaf0_GO9W3PKsnWWrwsu6JNoxQTP4zwX4mm0onnCY1YkP06iF879pJSlRSKeRyc8FzQv8mIV_f1i0VsY3dTD6MFrM5Jq9Dqu6316V7VGLeSTOcAw9_rPPEBLqgPo0XlSqbn35Dquse_JFudbHDScb5dhujEDkI0jlXNGavCoyHftb8iVPoy60zL81S9kM0qL4MLjXrtbR0xHrvA3WiQwKlIb67U0zqM1WsV77CxIb-xCLix0Pv6G1s0uvgwJ8k67I-iMfDajxR4mh2Fm66HXfjm7w-0CGMKcj9cvo2cd9A5fPZyn0dcP76_ry3i7u9jU1TaWSZr5uJVtVmIqueCKCpEVaVciK9tEgWpbxSjrypxzLFF0SQayVDSTRUlTQIFtJ5PT6O09d7Lm14zON4N2MqwMRjSza1jBE5rQICRE6X1UWuOcxa6ZrB7ALg2jzdF4E4w3R-NNljdH46HlzQN9bgdUjw3_FSf_AEujrfY</recordid><startdate>20161001</startdate><enddate>20161001</enddate><creator>Fuji, Shigeo</creator><creator>Inoue, Yoshitaka</creator><creator>Utsunomiya, Atae</creator><creator>Moriuchi, Yukiyoshi</creator><creator>Uchimaru, Kaoru</creator><creator>Choi, Ilseung</creator><creator>Otsuka, Eiichi</creator><creator>Henzan, Hideho</creator><creator>Kato, Koji</creator><creator>Tomoyose, Takeaki</creator><creator>Yamamoto, Hisashi</creator><creator>Kurosawa, Saiko</creator><creator>Matsuoka, Ken-Ichi</creator><creator>Yamaguchi, Takuhiro</creator><creator>Fukuda, Takahiro</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20161001</creationdate><title>Pretransplantation Anti-CCR4 Antibody Mogamulizumab Against Adult T-Cell Leukemia/Lymphoma Is Associated With Significantly Increased Risks of Severe and Corticosteroid-Refractory Graft-Versus-Host Disease, Nonrelapse Mortality, and Overall Mortality</title><author>Fuji, Shigeo ; Inoue, Yoshitaka ; Utsunomiya, Atae ; Moriuchi, Yukiyoshi ; Uchimaru, Kaoru ; Choi, Ilseung ; Otsuka, Eiichi ; Henzan, Hideho ; Kato, Koji ; Tomoyose, Takeaki ; Yamamoto, Hisashi ; Kurosawa, Saiko ; Matsuoka, Ken-Ichi ; Yamaguchi, Takuhiro ; Fukuda, Takahiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c346t-bcb69e4c252d055684f9e19b3dadbbd101f9722e9e5f36ac9d06c8904ae5ebfc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Acute Disease</topic><topic>Adrenal Cortex Hormones - therapeutic use</topic><topic>Adult</topic><topic>Aged</topic><topic>Antibodies, Monoclonal, Humanized - adverse effects</topic><topic>Antibodies, Monoclonal, Humanized - therapeutic use</topic><topic>Antineoplastic Combined Chemotherapy Protocols - adverse effects</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Databases, Factual</topic><topic>Female</topic><topic>Graft vs Host Disease - chemically induced</topic><topic>Graft vs Host Disease - drug therapy</topic><topic>Graft vs Host Disease - etiology</topic><topic>Graft vs Host Disease - immunology</topic><topic>Hematopoietic Stem Cell Transplantation - adverse effects</topic><topic>Hematopoietic Stem Cell Transplantation - methods</topic><topic>Humans</topic><topic>Leukemia-Lymphoma, Adult T-Cell - drug therapy</topic><topic>Leukemia-Lymphoma, Adult T-Cell - mortality</topic><topic>Leukemia-Lymphoma, Adult T-Cell - therapy</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Retrospective Studies</topic><topic>Survival Rate</topic><topic>Transplantation, Homologous</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fuji, Shigeo</creatorcontrib><creatorcontrib>Inoue, Yoshitaka</creatorcontrib><creatorcontrib>Utsunomiya, Atae</creatorcontrib><creatorcontrib>Moriuchi, Yukiyoshi</creatorcontrib><creatorcontrib>Uchimaru, Kaoru</creatorcontrib><creatorcontrib>Choi, Ilseung</creatorcontrib><creatorcontrib>Otsuka, Eiichi</creatorcontrib><creatorcontrib>Henzan, Hideho</creatorcontrib><creatorcontrib>Kato, Koji</creatorcontrib><creatorcontrib>Tomoyose, Takeaki</creatorcontrib><creatorcontrib>Yamamoto, Hisashi</creatorcontrib><creatorcontrib>Kurosawa, Saiko</creatorcontrib><creatorcontrib>Matsuoka, Ken-Ichi</creatorcontrib><creatorcontrib>Yamaguchi, Takuhiro</creatorcontrib><creatorcontrib>Fukuda, Takahiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fuji, Shigeo</au><au>Inoue, Yoshitaka</au><au>Utsunomiya, Atae</au><au>Moriuchi, Yukiyoshi</au><au>Uchimaru, Kaoru</au><au>Choi, Ilseung</au><au>Otsuka, Eiichi</au><au>Henzan, Hideho</au><au>Kato, Koji</au><au>Tomoyose, Takeaki</au><au>Yamamoto, Hisashi</au><au>Kurosawa, Saiko</au><au>Matsuoka, Ken-Ichi</au><au>Yamaguchi, Takuhiro</au><au>Fukuda, Takahiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pretransplantation Anti-CCR4 Antibody Mogamulizumab Against Adult T-Cell Leukemia/Lymphoma Is Associated With Significantly Increased Risks of Severe and Corticosteroid-Refractory Graft-Versus-Host Disease, Nonrelapse Mortality, and Overall Mortality</atitle><jtitle>Journal of clinical oncology</jtitle><addtitle>J Clin Oncol</addtitle><date>2016-10-01</date><risdate>2016</risdate><volume>34</volume><issue>28</issue><spage>3426</spage><epage>3433</epage><pages>3426-3433</pages><issn>0732-183X</issn><eissn>1527-7755</eissn><abstract>Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one important treatment option for patients with aggressive adult T-cell leukemia/lymphoma (ATLL). Mogamulizumab (anti-CCR4 monoclonal antibody; Mog) was recently approved as a treatment for ATLL in Japan. Major concerns exist about the possible adverse effects of pretransplantation Mog because Mog depletes regulatory T cells for several months. We assessed the impact of pretransplantation Mog on clinical outcomes after allo-HSCT.
We included 996 allo-HSCT recipients age 70 years or younger with aggressive ATLL who were given the diagnosis between 2000 and 2013 and who received intensive chemotherapy by multiple chemotherapeutic drugs as first-line therapy. Before allo-HSCT, 82 patients received Mog with a median interval of 45 days from the last Mog to allo-HSCT.
Pretransplantation Mog was associated with an increased risk of grade 3 to 4 acute graft-versus-host disease (GVHD; relative risk, 1.80; P < .01) and refractoriness to systemic corticosteroid for acute GVHD (relative risk, 2.09; P < .01). One-year cumulative incidence of nonrelapse mortality was significantly higher in patients with pretransplantation Mog compared with those without (43.7% v 25.1%; P < .01). The probability of 1-year overall survival was also significantly inferior in patients with pretransplantation Mog compared with those without (32.3% v 49.4%; P < .01). In particular, use of Mog with intervals < 50 days to allo-HSCT was associated with a dismal clinical outcome.
Pretransplantation Mog was significantly associated with an increased risk of GVHD-related mortality, which supports the relevance of CCR4-expressing Tregs after allo-HSCT in humans. In clinical practice, Mog should be cautiously used for patients with ATLL who are eligible for allo-HSCT.</abstract><cop>United States</cop><pmid>27507878</pmid><doi>10.1200/JCO.2016.67.8250</doi><tpages>8</tpages></addata></record> |
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| ispartof | Journal of clinical oncology, 2016-10, Vol.34 (28), p.3426-3433 |
| issn | 0732-183X 1527-7755 |
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| source | MEDLINE; American Society of Clinical Oncology Online Journals; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Acute Disease Adrenal Cortex Hormones - therapeutic use Adult Aged Antibodies, Monoclonal, Humanized - adverse effects Antibodies, Monoclonal, Humanized - therapeutic use Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - therapeutic use Databases, Factual Female Graft vs Host Disease - chemically induced Graft vs Host Disease - drug therapy Graft vs Host Disease - etiology Graft vs Host Disease - immunology Hematopoietic Stem Cell Transplantation - adverse effects Hematopoietic Stem Cell Transplantation - methods Humans Leukemia-Lymphoma, Adult T-Cell - drug therapy Leukemia-Lymphoma, Adult T-Cell - mortality Leukemia-Lymphoma, Adult T-Cell - therapy Male Middle Aged Retrospective Studies Survival Rate Transplantation, Homologous Young Adult |
| title | Pretransplantation Anti-CCR4 Antibody Mogamulizumab Against Adult T-Cell Leukemia/Lymphoma Is Associated With Significantly Increased Risks of Severe and Corticosteroid-Refractory Graft-Versus-Host Disease, Nonrelapse Mortality, and Overall Mortality |
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