Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma
Abstract Background Nivolumab, an anti-programmed cell death-1 monoclonal antibody, has improved the survival of patients with malignant melanoma. Despite its efficacy, nivolumab inconsistently induces thyroid dysfunction as an immune-related adverse event (irAE). This study aimed to evaluate nivolu...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-06-01
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| Series: | BMC Endocrine Disorders |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12902-018-0267-x |
| _version_ | 1818958479749021696 |
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| author | Seiichi Yano Kenji Ashida Hiromi Nagata Kenji Ohe Naoko Wada Yukina Takeichi Yuki Hanada Yuta Ibayashi Lixiang Wang Shohei Sakamoto Ryuichi Sakamoto Hiroshi Uchi Motoaki Shiratsuchi Masutaka Furue Masatoshi Nomura Yoshihiro Ogawa |
| author_facet | Seiichi Yano Kenji Ashida Hiromi Nagata Kenji Ohe Naoko Wada Yukina Takeichi Yuki Hanada Yuta Ibayashi Lixiang Wang Shohei Sakamoto Ryuichi Sakamoto Hiroshi Uchi Motoaki Shiratsuchi Masutaka Furue Masatoshi Nomura Yoshihiro Ogawa |
| author_sort | Seiichi Yano |
| collection | DOAJ |
| description | Abstract Background Nivolumab, an anti-programmed cell death-1 monoclonal antibody, has improved the survival of patients with malignant melanoma. Despite its efficacy, nivolumab inconsistently induces thyroid dysfunction as an immune-related adverse event (irAE). This study aimed to evaluate nivolumab-induced thyroid dysfunction to determine the risks and mechanisms of thyroid irAEs. Methods After excluding 10 patients, data of 24 patients with malignant melanoma (aged 17–85 years; 54% female) were retrospectively analyzed. Results Thyroid irAEs were observed in seven patients (29%). Three patients had hypothyroidism after preceding transient thyrotoxicosis, and the other four patients had hypothyroidism without thyrotoxicosis. Levothyroxine-Na replacement was required in three patients. Antithyroid antibody (ATA) titer was elevated in one of four assessable patients. The average (±SD) time to onset of thyroid irAE was 33.6 (±21.9) weeks. The administration period of nivolumab was longer in patients with thyroid irAEs than in those without thyroid irAEs (P < 0.01). There were no significant differences between patients with and without thyroid irAEs regarding age, sex, tumor stage, response to nivolumab therapy, baseline thyroid function, antithyroid peroxidase antibody (anti-TPO Ab) and antithyroglobulin antibody (anti-Tg Ab). Conclusions Thyroid dysfunction was a common irAE of nivolumab in malignant melanoma. Neither anti-TPO Ab nor anti-Tg Ab was associated with the risk for nivolumab-induced thyroid dysfunction. A conventional ATA-independent mechanism might be involved in thyroid irAEs. Further studies are required to clarify the mechanism and identify the predictive factors of thyroid irAEs. |
| first_indexed | 2024-12-20T11:26:24Z |
| format | Article |
| id | doaj.art-5bd2e9d380954684be3d0d0d2083d326 |
| institution | Directory Open Access Journal |
| issn | 1472-6823 |
| language | English |
| last_indexed | 2024-12-20T11:26:24Z |
| publishDate | 2018-06-01 |
| publisher | BMC |
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| series | BMC Endocrine Disorders |
| spelling | doaj.art-5bd2e9d380954684be3d0d0d2083d3262022-12-21T19:42:21ZengBMCBMC Endocrine Disorders1472-68232018-06-011811610.1186/s12902-018-0267-xNivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanomaSeiichi Yano0Kenji Ashida1Hiromi Nagata2Kenji Ohe3Naoko Wada4Yukina Takeichi5Yuki Hanada6Yuta Ibayashi7Lixiang Wang8Shohei Sakamoto9Ryuichi Sakamoto10Hiroshi Uchi11Motoaki Shiratsuchi12Masutaka Furue13Masatoshi Nomura14Yoshihiro Ogawa15Department of Medicine and Bioregulatory Science, Graduate School Of Medical Sciences, Kyushu UniversityDepartment of Medicine and Bioregulatory Science, Graduate School Of Medical Sciences, Kyushu UniversityDepartment of Medicine and Bioregulatory Science, Graduate School Of Medical Sciences, Kyushu UniversityFaculty of Pharmaceutical Sciences, Fukuoka UniversityDepartment of Dermatology, Kyushu University HospitalDepartment of Medicine and Bioregulatory Science, Graduate School Of Medical Sciences, Kyushu UniversityDepartment of Medicine and Bioregulatory Science, Graduate School Of Medical Sciences, Kyushu UniversityDepartment of Medicine and Bioregulatory Science, Graduate School Of Medical Sciences, Kyushu UniversityDepartment of Medicine and Bioregulatory Science, Graduate School Of Medical Sciences, Kyushu UniversityDepartment of Medicine and Bioregulatory Science, Graduate School Of Medical Sciences, Kyushu UniversityDepartment of Medicine and Bioregulatory Science, Graduate School Of Medical Sciences, Kyushu UniversityDepartment of Dermatology, Kyushu University HospitalDepartment of Medicine and Bioregulatory Science, Graduate School Of Medical Sciences, Kyushu UniversityDepartment of Dermatology, Kyushu University HospitalDivision of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of MedicineDepartment of Medicine and Bioregulatory Science, Graduate School Of Medical Sciences, Kyushu UniversityAbstract Background Nivolumab, an anti-programmed cell death-1 monoclonal antibody, has improved the survival of patients with malignant melanoma. Despite its efficacy, nivolumab inconsistently induces thyroid dysfunction as an immune-related adverse event (irAE). This study aimed to evaluate nivolumab-induced thyroid dysfunction to determine the risks and mechanisms of thyroid irAEs. Methods After excluding 10 patients, data of 24 patients with malignant melanoma (aged 17–85 years; 54% female) were retrospectively analyzed. Results Thyroid irAEs were observed in seven patients (29%). Three patients had hypothyroidism after preceding transient thyrotoxicosis, and the other four patients had hypothyroidism without thyrotoxicosis. Levothyroxine-Na replacement was required in three patients. Antithyroid antibody (ATA) titer was elevated in one of four assessable patients. The average (±SD) time to onset of thyroid irAE was 33.6 (±21.9) weeks. The administration period of nivolumab was longer in patients with thyroid irAEs than in those without thyroid irAEs (P < 0.01). There were no significant differences between patients with and without thyroid irAEs regarding age, sex, tumor stage, response to nivolumab therapy, baseline thyroid function, antithyroid peroxidase antibody (anti-TPO Ab) and antithyroglobulin antibody (anti-Tg Ab). Conclusions Thyroid dysfunction was a common irAE of nivolumab in malignant melanoma. Neither anti-TPO Ab nor anti-Tg Ab was associated with the risk for nivolumab-induced thyroid dysfunction. A conventional ATA-independent mechanism might be involved in thyroid irAEs. Further studies are required to clarify the mechanism and identify the predictive factors of thyroid irAEs.http://link.springer.com/article/10.1186/s12902-018-0267-xThyroidNivolumabThyroiditisHypothyroidismProgrammed cell death − 1 |
| spellingShingle | Seiichi Yano Kenji Ashida Hiromi Nagata Kenji Ohe Naoko Wada Yukina Takeichi Yuki Hanada Yuta Ibayashi Lixiang Wang Shohei Sakamoto Ryuichi Sakamoto Hiroshi Uchi Motoaki Shiratsuchi Masutaka Furue Masatoshi Nomura Yoshihiro Ogawa Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma BMC Endocrine Disorders Thyroid Nivolumab Thyroiditis Hypothyroidism Programmed cell death − 1 |
| title | Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma |
| title_full | Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma |
| title_fullStr | Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma |
| title_full_unstemmed | Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma |
| title_short | Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma |
| title_sort | nivolumab induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in japanese patients with malignant melanoma |
| topic | Thyroid Nivolumab Thyroiditis Hypothyroidism Programmed cell death − 1 |
| url | http://link.springer.com/article/10.1186/s12902-018-0267-x |
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