Prevalence of immune-related adverse events and anti-tumor efficacy following immune checkpoint inhibitor therapy in Japanese patients with various solid tumors
Abstract Background While immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (irAEs) in various organs, the prevalence of irAEs and potential risk factors have not been clarified. We identified irAE predictive factors and examined the relationship between the effect...
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BMC
2022-11-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-022-10327-7 |
| _version_ | 1811315178895048704 |
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| author | Yuki Yoshikawa Michio Imamura Masami Yamauchi C. Nelson Hayes Hiroshi Aikata Wataru Okamoto Yoshihiro Miyata Morihito Okada Noboru Hattori Kazuhiko Sugiyama Yukio Yoshioka Shigeaki Toratani Masaaki Takechi Tatsuo Ichinohe Tsutomu Ueda Sachio Takeno Tsuyoshi Kobayashi Hideki Ohdan Jun Teishima Michihiro Hide Yasushi Nagata Yoshiki Kudo Koji Iida Kazuaki Chayama |
| author_facet | Yuki Yoshikawa Michio Imamura Masami Yamauchi C. Nelson Hayes Hiroshi Aikata Wataru Okamoto Yoshihiro Miyata Morihito Okada Noboru Hattori Kazuhiko Sugiyama Yukio Yoshioka Shigeaki Toratani Masaaki Takechi Tatsuo Ichinohe Tsutomu Ueda Sachio Takeno Tsuyoshi Kobayashi Hideki Ohdan Jun Teishima Michihiro Hide Yasushi Nagata Yoshiki Kudo Koji Iida Kazuaki Chayama |
| author_sort | Yuki Yoshikawa |
| collection | DOAJ |
| description | Abstract Background While immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (irAEs) in various organs, the prevalence of irAEs and potential risk factors have not been clarified. We identified irAE predictive factors and examined the relationship between the effect of ICIs and irAEs for patients with malignancies. Methods A total of 533 cases treated with ICIs, including programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), for various malignancies were included retrospectively. We recorded irAEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 5. Prevalence and predictive factors associated with immune-related liver injury and the relationship between irAE and treatment response were analyzed. Results During a median of 10 (1–103) cycles with a median follow-up after several ICI initiations of 384 (21–1715) days, irAEs with all grades and with grade ≥ 3 developed in 144 (27.0%) and 57 (10.7%) cases. Cumulative irAE development rates were 21.9, 33.5, and 43.0% in all grades and 8.8, 14.9, and 20.7% in grade ≥ 3 at 5, 10, and 20 cycles, respectively. Patients who received anti-CTLA4 therapy were more likely to develop irAEs compared to those who received anti-PD-1 or anti-PD-L1 monotherapy. Liver injury was the most common irAE. Multivariate analysis identified the combination of PD-1 and anti-CTL-4 antibodies (hazard ratio [HR], 17.04; P < 0.0001) and baseline eosinophil count ≥130/μL (HR, 3.01 for < 130; P = 0.012) as independent risk factors for the incidence of immune-related liver injury with grade ≥ 2. Patients who developed irAEs had a higher disease control rate (P < 0.0001) and an increased overall survival rate compared to those without irAEs (P < 0.0001). Conclusion Combination therapy with anti-PD-1 and anti-CTL-4 antibodies resulted in higher a frequency of irAEs. Baseline absolute eosinophil count was found to be a predictive factor for immune-related liver injury. Occurrence of irAEs may be associated with higher efficacy of ICI treatment and longer survival among patients who receive ICI therapy. |
| first_indexed | 2024-04-13T11:25:33Z |
| format | Article |
| id | doaj.art-9db6981ec3ff4d57acfc8ee546284f44 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T11:25:33Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-9db6981ec3ff4d57acfc8ee546284f442022-12-22T02:48:42ZengBMCBMC Cancer1471-24072022-11-012211910.1186/s12885-022-10327-7Prevalence of immune-related adverse events and anti-tumor efficacy following immune checkpoint inhibitor therapy in Japanese patients with various solid tumorsYuki Yoshikawa0Michio Imamura1Masami Yamauchi2C. Nelson Hayes3Hiroshi Aikata4Wataru Okamoto5Yoshihiro Miyata6Morihito Okada7Noboru Hattori8Kazuhiko Sugiyama9Yukio Yoshioka10Shigeaki Toratani11Masaaki Takechi12Tatsuo Ichinohe13Tsutomu Ueda14Sachio Takeno15Tsuyoshi Kobayashi16Hideki Ohdan17Jun Teishima18Michihiro Hide19Yasushi Nagata20Yoshiki Kudo21Koji Iida22Kazuaki Chayama23Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima UniversityDepartment of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima UniversityDepartment of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima UniversityDepartment of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima UniversityDepartment of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima UniversityCancer Treatment Center, Hiroshima University HospitalDepartment of Surgical Oncology, Hiroshima UniversityDepartment of Surgical Oncology, Hiroshima UniversityDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Clinical Oncology, Hiroshima University HospitalDepartment of Molecular Oral Medicine and Maxillofacial Surgery, Graduate School of Biomedical and Health Science, Hiroshima UniversityDepartment of Molecular Oral Medicine and Maxillofacial Surgery, Graduate School of Biomedical and Health Science, Hiroshima UniversityDepartment of Oral and Maxillofacial Surgery, Program of Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima UniversityDepartment of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima UniversityDepartment of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima UniversityDepartment of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Dermatology, Graduate School of Biomedical and Sciences, Hiroshima UniversityDepartment of Radiation Oncology, Hiroshima University HospitalDepartment of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Hiroshima UniversityDepartment of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima UniversityAbstract Background While immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (irAEs) in various organs, the prevalence of irAEs and potential risk factors have not been clarified. We identified irAE predictive factors and examined the relationship between the effect of ICIs and irAEs for patients with malignancies. Methods A total of 533 cases treated with ICIs, including programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), for various malignancies were included retrospectively. We recorded irAEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 5. Prevalence and predictive factors associated with immune-related liver injury and the relationship between irAE and treatment response were analyzed. Results During a median of 10 (1–103) cycles with a median follow-up after several ICI initiations of 384 (21–1715) days, irAEs with all grades and with grade ≥ 3 developed in 144 (27.0%) and 57 (10.7%) cases. Cumulative irAE development rates were 21.9, 33.5, and 43.0% in all grades and 8.8, 14.9, and 20.7% in grade ≥ 3 at 5, 10, and 20 cycles, respectively. Patients who received anti-CTLA4 therapy were more likely to develop irAEs compared to those who received anti-PD-1 or anti-PD-L1 monotherapy. Liver injury was the most common irAE. Multivariate analysis identified the combination of PD-1 and anti-CTL-4 antibodies (hazard ratio [HR], 17.04; P < 0.0001) and baseline eosinophil count ≥130/μL (HR, 3.01 for < 130; P = 0.012) as independent risk factors for the incidence of immune-related liver injury with grade ≥ 2. Patients who developed irAEs had a higher disease control rate (P < 0.0001) and an increased overall survival rate compared to those without irAEs (P < 0.0001). Conclusion Combination therapy with anti-PD-1 and anti-CTL-4 antibodies resulted in higher a frequency of irAEs. Baseline absolute eosinophil count was found to be a predictive factor for immune-related liver injury. Occurrence of irAEs may be associated with higher efficacy of ICI treatment and longer survival among patients who receive ICI therapy.https://doi.org/10.1186/s12885-022-10327-7Immune checkpoint inhibitorsImmune-related adverse eventsImmune-related liver injuryProgrammed death 1Cytotoxic T-lymphocyte antigen 4Combination therapy |
| spellingShingle | Yuki Yoshikawa Michio Imamura Masami Yamauchi C. Nelson Hayes Hiroshi Aikata Wataru Okamoto Yoshihiro Miyata Morihito Okada Noboru Hattori Kazuhiko Sugiyama Yukio Yoshioka Shigeaki Toratani Masaaki Takechi Tatsuo Ichinohe Tsutomu Ueda Sachio Takeno Tsuyoshi Kobayashi Hideki Ohdan Jun Teishima Michihiro Hide Yasushi Nagata Yoshiki Kudo Koji Iida Kazuaki Chayama Prevalence of immune-related adverse events and anti-tumor efficacy following immune checkpoint inhibitor therapy in Japanese patients with various solid tumors BMC Cancer Immune checkpoint inhibitors Immune-related adverse events Immune-related liver injury Programmed death 1 Cytotoxic T-lymphocyte antigen 4 Combination therapy |
| title | Prevalence of immune-related adverse events and anti-tumor efficacy following immune checkpoint inhibitor therapy in Japanese patients with various solid tumors |
| title_full | Prevalence of immune-related adverse events and anti-tumor efficacy following immune checkpoint inhibitor therapy in Japanese patients with various solid tumors |
| title_fullStr | Prevalence of immune-related adverse events and anti-tumor efficacy following immune checkpoint inhibitor therapy in Japanese patients with various solid tumors |
| title_full_unstemmed | Prevalence of immune-related adverse events and anti-tumor efficacy following immune checkpoint inhibitor therapy in Japanese patients with various solid tumors |
| title_short | Prevalence of immune-related adverse events and anti-tumor efficacy following immune checkpoint inhibitor therapy in Japanese patients with various solid tumors |
| title_sort | prevalence of immune related adverse events and anti tumor efficacy following immune checkpoint inhibitor therapy in japanese patients with various solid tumors |
| topic | Immune checkpoint inhibitors Immune-related adverse events Immune-related liver injury Programmed death 1 Cytotoxic T-lymphocyte antigen 4 Combination therapy |
| url | https://doi.org/10.1186/s12885-022-10327-7 |
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