The incorporation of immune checkpoint inhibitors in the oncologists' arsenal is a milestone in cancer therapeutics, though not being devoid of toxicities.Areas covered: The present review provides a comprehensive and up-to-date overview of the immune-related hypophysitis with focus on the elusive biological background, the wide spectrum of the epidemiological profile, the varying clinical aspects, and the diagnostic and therapeutic challenges.Expert opinion: Historically considered distinctive of anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibodies (mAbs), the immune-related hypophysitis is increasingly correlated with the anti-programmed cell-death (PD) protein 1 (PD-1)/anti-PD ligand 1 (PD-L1) mAbs. The distinct phenotype of hypophysitis related to anti-PD1/anti-PD-L1 mAbs is highlighted with focus on the immune-related isolated adrenocorticotropic (ACTH) deficiency. The immune-related central diabetes insipidus is discussed as a rare aspect of anti-CTL-A4 mAbs-induced hypophysitis, recently related to anti-PD1/anti-PD-L1 mAbs as well. The present review builds on existing literature concerning immune-related hypophysitis underscoring the pending issues still to be addressed, including (i) pathogenesis; (ii) correlation with preexisting autoimmunity; (iii) predictive value; (iv) utility of high-dose glucocorticoids; and (v) establishment of evidence-based diagnostic and therapeutic protocols. Increased awareness and constant vigilance are advocated as cornerstone of a multidisciplinary approach to ensure optimal patients' care.
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http://dx.doi.org/10.1080/14712598.2021.1869211 | DOI Listing |
EJHaem
December 2024
Division of Hematology and Oncology, Department of Medicine University of Washington Seattle Washington USA.
Background: The tumor microenvironment (TME), including infiltrating T-cells, is thought to play a major role in the pathogenesis and prognosis of follicular lymphoma (FL) and may contribute to its widely varied disease course. We hypothesized that programmed death-1 inhibition may be most effective in untreated, immunocompetent FL patients. Thus, we developed a phase 2 study to evaluate the efficacy of pembrolizumab as the initial treatment for indolent B-cell lymphoma.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Oncology, Oslo University Hospital, Oslo, Norway.
Background: Pleural mesothelioma (PM) is a rare cancer with a dismal prognosis. Dual immune checkpoint inhibitors have improved overall survival, but the rate of immune-related adverse events (irAEs) is high. Serum cytokines reflect systemic immune reactions and may serve as biomarkers for irAEs.
View Article and Find Full Text PDFMod Pathol
December 2024
Department of Pathology and Molecular Pathology, University Hospital of Zurich, Switzerland; University of Zurich, Switzerland.
While immune checkpoint inhibitors (ICIs) have revolutionized modern oncology, they are also associated with immune-related adverse events (irAEs). Previous histopathological descriptions of organ-related inflammatory changes do not consider systemic effects of ICIs, because of an absence of comprehensive autopsy studies. We performed a retrospective study on 42 whole-body autopsies of patients treated with ICIs from January 2011 to March 2024 to determine frequency, organ distribution and morphology of ICIs-associated inflammatory changes as well as their clinical relevance.
View Article and Find Full Text PDFCrit Rev Oncol Hematol
December 2024
Center for Clinical Investigation, INSERM U1434, Strasbourg University, 1 Avenue Molière, Strasbourg 67098, France; Neurology Department, Strasbourg University Hospitals, 1 Avenue Molière, Strasbourg 67098, France. Electronic address:
The ever-increasing use of immune checkpoint inhibitors (ICIs) has significantly improved cancer management, but at the cost of frequent immunologic side effects. Among them, neurologic immune-related adverse events (nirAEs) are less common but pose a challenge to clinicians due to their severity, heterogeneous nature and nonspecific clinical presentation, making diagnosis complex. The prognosis of these nirAEs, especially those related to the central nervous system (CNS), correlates with their rapid recognition and therapeutic management.
View Article and Find Full Text PDFEndocr Connect
November 2024
Department of Endocrinology, University Hospital Plymouth, UK.
Introduction: The aim of this study was to define functional and anatomical pituitary disease at the time of presentation following immune checkpoint inhibitor (ICI) therapy and to describe any changes in pituitary function over time.
Methods: We conducted a retrospective observational audit of patients on ICI therapy at our centre between January 2013 and September 2023. We reviewed all patients on ICI therapy under the care of the oncology department at University Hospital Plymouth, a 1000-bedded hospital serving a population of 500,000 people.
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