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

Abstract

Immunotherapy has dramatically changed the therapeutic landscape of oncology, and has become standard of care in multiple cancer types in front or late lines of therapy, with some longstanding responses and outstanding results. Notwithstanding, its use has brought a totally unique spectrum of adverse events, characterized by a myriad of diverse manifestations affecting nearly every organ and system of the body, including the endocrine, nervous, cardiac, respiratory and gastrointestinal systems. Uncommon adverse events, defined as those occurring in less than 1% of patients, comprise an even more heterogeneous group of diseases that are being seen more recurrently as the use of immune check-point inhibitors increases and indications spread in different tumor types and stages. Here, we comprehensively review some uncommon, but exceedingly important, immune-related adverse events, with special emphasis in the clinical approach and diagnostic workup, aiming to reunite the evidence published previously, allowing an increase in awareness and knowledge from all specialists implicated in the diagnosis, treatment, and care of cancer patients treated with immunotherapy.

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

“…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 ].…”

“…Diagnostic work-up involves a thorough autoimmune panel, including anti-nuclear antibodies, anti-mitochondrial antibodies and anti-nuclear cytoplasmic antibodies, as well as IgG4 levels. Diagnostic imaging using CT or MRI to visualise the liver and biliary tree is also useful [ 81 , 82 ]. In cases involving large, extrahepatic bile ducts, imaging findings can include segmental or diffuse non-obstructive dilation and stenosis of the biliary duct lumen.…”

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

“…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.)…”

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

“…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.…”