Immune-Related Uncommon Adverse Events in Patients with Cancer Treated with Immunotherapy

Albarrán-Artahona, Víctor; Laguna, Juan-Carlos; Gorría, Teresa; Torres-Jiménez, Javier; Pascal, Mariona; Mezquita, Laura

doi:10.3390/diagnostics12092091

Cited by 7 publications

(17 citation statements)

References 232 publications

(323 reference statements)

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“…Clinical features are similar to other cholangitis-type syndromes, including right upper quadrant pain, fever and jaundice. Patients are usually symptomatic, although rare cases of asymptomatic bilirubin and cholestatic liver enzyme elevations have been described [ 82 ]. Important differential diagnoses to rule out include other autoimmune conditions such as primary sclerosing cholangitis, primary biliary cirrhosis and IgG4 disease, as well as infectious and malignant aetiologies [ 81 ].…”

Section: Other Rare Toxicitiesmentioning

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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Section: Other Rare Toxicitiesmentioning

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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show abstract

“…It is important to distinguish between the myositis-specified antibodies mentioned above from myositis-associated ones (anti-Ro/SSA, anti-DNAPK, anti-PM-Scl, and anti-Scl70), which characterize overlapping syndromes such as systemic sclerosis and anti-synthetase syndrome (e.g., antibodies against histidyl-transfer-RNA-synthetase (anti Jo-1)) [ 45 ]. The former is extremely rare, and there are only two case reports of patients with limited and diffuse skin involvement and an absence of autoantibodies; thus, the diagnosis was established based on clinical symptoms (fatigue, muscle weakness, skin tightness, etc.)…”

Section: Clinical Characteristics and Management Of The Rheumatic Adv...mentioning

confidence: 99%

Immune Checkpoint Inhibitor Related Rheumatological Complications: Cooperation between Rheumatologists and Oncologists

Pacholczak-Madej

Kosałka-Węgiel

Kuszmiersz

et al. 2023

IJERPH

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In cancer, immune checkpoint inhibitors (ICIs) improve patient survival but may lead to severe immune-related adverse events (irAEs). Rheumatic irAEs are a distinct entity that are much more common in a real-life than in clinical trial reports due to their unspecific symptoms and them being a rare cause of hospitalization. This review focuses on an interdisciplinary approach to the management of rheumatic irAEs, including cooperation between oncologists, rheumatologists, and immunologists. We discuss the immunological background of rheumatic irAEs, as well as their unique clinical characteristics, differentiation from other irAEs, and treatment strategies. Importantly, steroids are not the basis of therapy, and nonsteroidal anti-inflammatory drugs should be administered in the front line with other antirheumatic agents. We also address whether patients with pre-existing rheumatic autoimmune diseases can receive ICIs and how antirheumatic agents can interfere with ICIs. Interestingly, there is a preclinical rationale for combining ICIs with immunosuppressants, particularly tumor necrosis factor α and interleukin 6 inhibitors. Regardless of the data, the mainstay in managing irAEs is interdisciplinary cooperation between oncologists and other medical specialties.

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“…They work by blocking the negative regulatory factors that impede T cell activity, thereby activating T cells and harnessing the body’s innate immune response to fight cancer. They systematically bolster the body’s immune response against tumors, resulting in a marked enhancement of cancer patients’ overall survival rates ( 1 – 3 ). Presently, immune checkpoint inhibitors, with programmed death-1 (PD-1) inhibitors as a prominent example, have shown significant therapeutic effects in the treatment of various malignant tumors, benefiting an increasing number of cancer patients.…”

Section: Introductionmentioning

confidence: 99%

The risk of endocrine immune-related adverse events induced by PD-1 inhibitors in cancer patients: a systematic review and meta-analysis

Zhao,

et al. 2024

Front. Oncol.

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ObjectiveEndocrinopathies are the most common immune-related adverse events (irAEs) observed during therapy with PD-1 inhibitors. In this study, we conducted a comprehensive systematic review and meta-analysis to evaluate the risk of immune-related endocrinopathies in patients treated with PD-1 inhibitors.MethodsWe performed a systematic search in the PubMed, Embase, and Cochrane Library databases to retrieve all randomized controlled trials (RCTs) involving PD-1 inhibitors, spanning from their inception to November 24, 2023. The comparative analysis encompassed patients undergoing chemotherapy, targeted therapy, or receiving placebo as control treatments. This study protocol has been registered with PROSPERO (CRD42023488303).ResultsA total of 48 clinical trials comprising 24,514 patients were included. Compared with control groups, patients treated with PD-1 inhibitors showed an increased risk of immune-related adverse events, including hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, diabetes mellitus, and adrenal insufficiency. Pembrolizumab was associated with an increased risk of all aforementioned endocrinopathies (hypothyroidism: RR=4.76, 95%CI: 3.55-6.39; hyperthyroidism: RR=9.69, 95%CI: 6.95-13.52; hypophysitis: RR=5.47, 95%CI: 2.73-10.97; thyroiditis: RR=5.95, 95%CI: 3.02-11.72; diabetes mellitus: RR=3.60, 95%CI: 1.65-7.88; adrenal insufficiency: RR=4.80, 95%CI: 2.60-8.88). Nivolumab was associated with an increased risk of hypothyroidism (RR=7.67, 95%CI: 5.00-11.75) and hyperthyroidism (RR=9.22, 95%CI: 4.71-18.04). Tislelizumab and sintilimab were associated with an increased risk of hypothyroidism (RR=19.07, 95%CI: 5.46-66.69 for tislelizumab and RR=18.36, 95%CI: 3.58-94.21 for sintilimab). For different tumor types, both hypothyroidism and hyperthyroidism were at high risks. Besides, patients with non-small cell lung cancer were at a higher risk of thyroiditis and adrenal insufficiency. Patients with melanoma were at a higher risk of hypophysitis and diabetes mellitus. Both low- and high-dose group increased risks of hypothyroidism and hyperthyroidism.ConclusionRisk of endocrine irAEs may vary in different PD-1 inhibitors and different tumor types. Increased awareness and understanding of the risk features of endocrine irAEs associated with PD-1 inhibitors is critical for clinicians.Systematic review registrationcrd.york.ac.uk/prospero, identifier PROSPERO (CRD42023488303).

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Immune-Related Uncommon Adverse Events in Patients with Cancer Treated with Immunotherapy

Cited by 7 publications

References 232 publications

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

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

Immune Checkpoint Inhibitor Related Rheumatological Complications: Cooperation between Rheumatologists and Oncologists

The risk of endocrine immune-related adverse events induced by PD-1 inhibitors in cancer patients: a systematic review and meta-analysis

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