Hemophagocytic Lymphohistiocytosis Associated with Immunological Checkpoint Inhibitors: A Pharmacovigilance Study

Diaz, Laurine; Jauzelon, Benjamin; Dillies, Anne-Charlotte; Souder, Cosette Le; Faillie, Jean‐Luc; Maria, A.; Palassin, Pascale

doi:10.3390/jcm12051985

Cited by 13 publications

(10 citation statements)

References 53 publications

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“…According to the HLH-2004 and Hscore diagnostic criteria, common symptoms in patients with HLH include fever and splenomegaly ( 123 , 124 ). Typical laboratory findings include 2 or 3 lineages of peripheral blood cytopenias, hypertriglyceridemia, hypofibrinogenemia, elevated serum ferritin, and sCD25 ( 125 ). The biopsy can reveal hemophagocytosis in the bone marrow, spleen, or lymph nodes ( 126 ).…”

Section: Etiology Of Fever Of Unknown Origin Induced By Icismentioning

confidence: 99%

Fever of unknown origin associated with immune checkpoint inhibitors

Tong,

Zhan,

Dong

et al. 2024

Front. Immunol.

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Since the approval for the treatment of melanoma in 2014, immune checkpoint inhibitors (ICIs) have revolutionized the therapy pattern across various malignancies. Coinciding with their frequent usage, their adverse effects, including fever, cannot be neglected. In the context of cancer diseases and cancer treatments, fever of unknown origin (FUO), which has long posed a challenge for clinicians in terms of diagnosis and management, brings forth new connotation and significance. In this paper review, we present the concept of ICIs-associated FUO, consider activated immune system and elevated cytokines as common mechanisms by which ICIs induce fever and various immune-related adverse events (irAEs), summarize and compare the primary etiologies of ICI-associated FUO, and compare it with conventional types of FUO.

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Section: Etiology Of Fever Of Unknown Origin Induced By Icismentioning

confidence: 99%

Fever of unknown origin associated with immune checkpoint inhibitors

Tong,

Zhan,

Dong

et al. 2024

Front. Immunol.

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“…Patients typically present with fever, organomegaly, pancytopenia, significantly elevated ferritin and low fibrinogen. Features of haemophagocytosis may be evident on bone marrow aspiration, but not universally [ 62 , 63 ]. The diagnosis of HLH is often delayed due to lack of clinician awareness of the condition as well as overlapping differential diagnoses with similar symptoms and laboratory abnormalities.…”

Section: Haematological Toxicitymentioning

confidence: 99%

Rare Immune-Related Adverse Events (irAEs): Approach to Diagnosis and Management

Javaid,

Bennett,

Rao

et al. 2024

Pharm Med

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Immune checkpoint inhibitors (ICIs) have revolutionised the treatment landscape across many solid organ malignancies and form part of routine clinical practice in many tumours. As indications for monotherapy, doublet therapy and combination approaches with chemotherapy and targeted agents expand, clinicians must be aware of the wide range of possible immune-related adverse events (irAEs). Common toxicities, including rash, colitis, hepatitis and pneumonitis are well described in the literature, and have established diagnostic and management algorithms. Rarer toxicities, often with an incidence of less than 1%, are less defined. These syndromes can be poorly recognised, may take on a fulminant course and do not have established or evidence-based diagnostic and management strategies. As such, patients may experience increased morbidity, mortality and poorer outcomes, related both to these irAEs as well as how the treatment of these may affect the management of their underlying malignancy. In this review, we aim to explore the incidence, potential biomarkers, pathogenesis, diagnostic work-up and clinical sequelae of a selection of uncommon irAEs, with a focus on myocarditis, neurological and haematologic syndromes. Further prospective research is required to accurately define the incidence and pathogenesis of these conditions, with the aim of increasing clinician awareness of rare irAEs and to assist with a more personalised and mechanism-based approach to these syndromes.

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“…Hemophagocytic lymphohistiocytosis (HLH) is less common and, in contrast to other hematological irAEs, is more frequently linked to anti-CTLA4 treatment [139,142,145]. HLH also differs from other hematological toxicities due to the high mortality rate despite immunosuppressive treatment [139].…”

Section: Hematological Iraesmentioning

confidence: 99%

Immune-Related Adverse Events Due to Cancer Immunotherapy: Immune Mechanisms and Clinical Manifestations

Casagrande,

Sopetto,

Bertalot

et al. 2024

Cancers

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The landscape of cancer treatment has undergone a significant transformation with the introduction of Immune Checkpoint Inhibitors (ICIs). Patients undergoing these treatments often report prolonged clinical and radiological responses, albeit with a potential risk of developing immune-related adverse events (irAEs). Here, we reviewed and discussed the mechanisms of action of ICIs and their pivotal role in regulating the immune system to enhance the anti-tumor immune response. We scrutinized the intricate pathogenic mechanisms responsible for irAEs, arising from the evasion of self-tolerance checkpoints due to drug-induced immune modulation. We also summarized the main clinical manifestations due to irAEs categorized by organ types, detailing their incidence and associated risk factors. The occurrence of irAEs is more frequent when ICIs are combined; with neurological, cardiovascular, hematological, and rheumatic irAEs more commonly linked to PD1/PD-L1 inhibitors and cutaneous and gastrointestinal irAEs more prevalent with CTLA4 inhibitors. Due to the often-nonspecific signs and symptoms, the diagnosis of irAEs (especially for those rare ones) can be challenging. The differential with primary autoimmune disorders becomes sometimes intricate, given the clinical and pathophysiological similarities. In conclusion, considering the escalating use of ICIs, this area of research necessitates additional clinical studies and practical insights, especially the development of biomarkers for predicting immune toxicities. In addition, there is a need for heightened education for both clinicians and patients to enhance understanding and awareness.

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Hemophagocytic Lymphohistiocytosis Associated with Immunological Checkpoint Inhibitors: A Pharmacovigilance Study

Cited by 13 publications

References 53 publications

Fever of unknown origin associated with immune checkpoint inhibitors

Fever of unknown origin associated with immune checkpoint inhibitors

Rare Immune-Related Adverse Events (irAEs): Approach to Diagnosis and Management

Immune-Related Adverse Events Due to Cancer Immunotherapy: Immune Mechanisms and Clinical Manifestations

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