Targeted inhibition of the IL5 axis for immune checkpoint inhibitors eosinophilic-induced adverse events
Given the broad implementation of immune checkpoint inhibitors (ICI) for cancer therapy, we encounter a variety of immune-related adverse events (irAE) including immune-related blood eosinophilia. Eosinophilia demonstrated a potential positive predictive marker for a beneficial clinical response to...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/10/e009658.full |
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| author | Michal Lotem Limor Rubin Aviv Talmon Yaarit Ribak David Lavie Hovav Nechushtan Nadia Caplan Oded Shamriz Irit Adini Yuval Tal |
| author_facet | Michal Lotem Limor Rubin Aviv Talmon Yaarit Ribak David Lavie Hovav Nechushtan Nadia Caplan Oded Shamriz Irit Adini Yuval Tal |
| author_sort | Michal Lotem |
| collection | DOAJ |
| description | Given the broad implementation of immune checkpoint inhibitors (ICI) for cancer therapy, we encounter a variety of immune-related adverse events (irAE) including immune-related blood eosinophilia. Eosinophilia demonstrated a potential positive predictive marker for a beneficial clinical response to ICI. However, there are reports of eosinophil-induced adverse events (Eo-irAE) with organ dysfunction requiring initiation of oral glucocorticoid therapy and discontinuation of ICI.We aim to assess the efficacy and safety of interleukin (IL) 5-axis inhibition in Eo-irAE secondary to ICI therapy.We present three cases of Eo-irAE referred to our allergy and clinical immunology unit at Hadassah Hebrew University Medical Center following therapy with pembrolizumab and nivolumab, monoclonal antibodies that target the programmed cell death 1 (PD-1) receptor, for two cases of melanoma and one metastatic non-small cell lung carcinoma. Following informed consent and committee approval, two patients were treated with 1–3 doses of mepolizumab, 100 mg, monoclonal IgG1 kappa anti-IL-5 antibody, and one patient received up-to-date 9 doses of benralizumab, 30 mg, monoclonal IgG1 kappa antibody directed against the alpha chain of the interleukin-5 receptor, both administered subcutaneously. Patients were carefully followed and treatment response was assessed by physical examinations and laboratory tests.Hypereosinophilia at the level of 2300–8000 K/UL was observed 8–12 months following therapy accompanied by symptoms of dyspnea, arthralgia, myalgia, fasciitis, ‘morphea’-like lesions, fatigue, abdominal discomfort, pruritus, and chest pain. ICI discontinuation did not improve symptoms, two patients were resistant to glucocorticoids and therefore biological treatment was initiated to inhibit the IL5 axis. Patients demonstrated rapid clinical response and a decrease in peripheral blood eosinophil levels with long-term symptoms remission. There were no signals of negative impacts, such as tumor progression following IL5 axis inhibition.Eosinophilia secondary to ICI therapy can lead to organ dysfunction. Discontinuation of ICI might not be effective and symptoms may be refractory to steroid therapy hence targeted inhibition of the IL5 axis should be considered. |
| format | Article |
| id | doaj-art-f6e42c9984c04b73a8c8df5cf2496e0f |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-f6e42c9984c04b73a8c8df5cf2496e0f2025-08-20T02:14:23ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-10-01121010.1136/jitc-2024-009658Targeted inhibition of the IL5 axis for immune checkpoint inhibitors eosinophilic-induced adverse eventsMichal Lotem0Limor Rubin1Aviv Talmon2Yaarit Ribak3David Lavie4Hovav Nechushtan5Nadia Caplan6Oded Shamriz7Irit Adini8Yuval Tal9Sharett Institute of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, IsraelAllergy and Clinical Immunology Unit, Department of Medicine, Hadassah University Medical Center Division of Internal Medicine, Jerusalem, IsraelAllergy and Clinical Immunology Unit, Department of Medicine, Hadassah University Medical Center Division of Internal Medicine, Jerusalem, IsraelAllergy and Clinical Immunology Unit, Department of Medicine, Hadassah University Medical Center Division of Internal Medicine, Jerusalem, IsraelDepartment of Hematology, Hadassah University Medical Center, Jerusalem, IsraelOncology, Hadassah Medical Center, Jerusalem, IsraelDepartment of Radiology, Hadassah University Medical Center, Jerusalem, IsraelAllergy and Clinical Immunology Unit, Department of Medicine, Hadassah University Medical Center, Jerusalem, IsraelDepartment of Surgery, Center for Engineering in Medicine and Surgery, Harvard Medical School, Boston, Massachusetts, USAAllergy and Clinical Immunology Unit, Department of Medicine, Hadassah University Medical Center Division of Internal Medicine, Jerusalem, IsraelGiven the broad implementation of immune checkpoint inhibitors (ICI) for cancer therapy, we encounter a variety of immune-related adverse events (irAE) including immune-related blood eosinophilia. Eosinophilia demonstrated a potential positive predictive marker for a beneficial clinical response to ICI. However, there are reports of eosinophil-induced adverse events (Eo-irAE) with organ dysfunction requiring initiation of oral glucocorticoid therapy and discontinuation of ICI.We aim to assess the efficacy and safety of interleukin (IL) 5-axis inhibition in Eo-irAE secondary to ICI therapy.We present three cases of Eo-irAE referred to our allergy and clinical immunology unit at Hadassah Hebrew University Medical Center following therapy with pembrolizumab and nivolumab, monoclonal antibodies that target the programmed cell death 1 (PD-1) receptor, for two cases of melanoma and one metastatic non-small cell lung carcinoma. Following informed consent and committee approval, two patients were treated with 1–3 doses of mepolizumab, 100 mg, monoclonal IgG1 kappa anti-IL-5 antibody, and one patient received up-to-date 9 doses of benralizumab, 30 mg, monoclonal IgG1 kappa antibody directed against the alpha chain of the interleukin-5 receptor, both administered subcutaneously. Patients were carefully followed and treatment response was assessed by physical examinations and laboratory tests.Hypereosinophilia at the level of 2300–8000 K/UL was observed 8–12 months following therapy accompanied by symptoms of dyspnea, arthralgia, myalgia, fasciitis, ‘morphea’-like lesions, fatigue, abdominal discomfort, pruritus, and chest pain. ICI discontinuation did not improve symptoms, two patients were resistant to glucocorticoids and therefore biological treatment was initiated to inhibit the IL5 axis. Patients demonstrated rapid clinical response and a decrease in peripheral blood eosinophil levels with long-term symptoms remission. There were no signals of negative impacts, such as tumor progression following IL5 axis inhibition.Eosinophilia secondary to ICI therapy can lead to organ dysfunction. Discontinuation of ICI might not be effective and symptoms may be refractory to steroid therapy hence targeted inhibition of the IL5 axis should be considered.https://jitc.bmj.com/content/12/10/e009658.full |
| spellingShingle | Michal Lotem Limor Rubin Aviv Talmon Yaarit Ribak David Lavie Hovav Nechushtan Nadia Caplan Oded Shamriz Irit Adini Yuval Tal Targeted inhibition of the IL5 axis for immune checkpoint inhibitors eosinophilic-induced adverse events Journal for ImmunoTherapy of Cancer |
| title | Targeted inhibition of the IL5 axis for immune checkpoint inhibitors eosinophilic-induced adverse events |
| title_full | Targeted inhibition of the IL5 axis for immune checkpoint inhibitors eosinophilic-induced adverse events |
| title_fullStr | Targeted inhibition of the IL5 axis for immune checkpoint inhibitors eosinophilic-induced adverse events |
| title_full_unstemmed | Targeted inhibition of the IL5 axis for immune checkpoint inhibitors eosinophilic-induced adverse events |
| title_short | Targeted inhibition of the IL5 axis for immune checkpoint inhibitors eosinophilic-induced adverse events |
| title_sort | targeted inhibition of the il5 axis for immune checkpoint inhibitors eosinophilic induced adverse events |
| url | https://jitc.bmj.com/content/12/10/e009658.full |
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