Targeted inhibition of the IL5 axis for immune checkpoint inhibitors eosinophilic-induced adverse events.

Autor:	Rubin L; Allergy and Clinical Immunology Unit, Department of Medicine, Hadassah University Medical Center Division of Internal Medicine, Jerusalem, Israel limorlaz@gmail.com., Talmon A; Allergy and Clinical Immunology Unit, Department of Medicine, Hadassah University Medical Center Division of Internal Medicine, Jerusalem, Israel., Ribak Y; Allergy and Clinical Immunology Unit, Department of Medicine, Hadassah University Medical Center Division of Internal Medicine, Jerusalem, Israel., Lavie D; Department of Hematology, Hadassah University Medical Center, Jerusalem, Israel., Nechushtan H; Oncology, Hadassah Medical Center, Jerusalem, Israel.; Hebrew University, Jerusalem, Israel., Caplan N; Department of Radiology, Hadassah University Medical Center, Jerusalem, Israel., Lotem M; Oncology, Hadassah Medical Center, Jerusalem, Israel., Shamriz O; Allergy and Clinical Immunology Unit, Department of Medicine, Hadassah University Medical Center, Jerusalem, Israel.; Institute of Medical Research Israel-Canada, Faculty of Medicine, Hebrew University The Lautenberg Center for Immunology and Cancer, Jerusalem, Israel., Adini I; Department of Surgery, Center for Engineering in Medicine and Surgery, Harvard Medical School, Boston, Massachusetts, USA., Tal Y; Allergy and Clinical Immunology Unit, Department of Medicine, Hadassah University Medical Center Division of Internal Medicine, Jerusalem, Israel.
Jazyk:	angličtina
Zdroj:	Journal for immunotherapy of cancer [J Immunother Cancer] 2024 Oct 12; Vol. 12 (10). Date of Electronic Publication: 2024 Oct 12.
DOI:	10.1136/jitc-2024-009658
Abstrakt:	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. Competing Interests: Competing interests: No, there are no competing interests. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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