Immune-related adverse events in patients with solid-organ tumours treated with immunotherapy: a 3-year study of 102 cases from a single centre

Abstract

ObjectiveImmune checkpoint blockade therapy (ICBT) increases the anti-tumoural function of the immune system, but it can also induce immune-related adverse events (irAEs). Our aim was to assess the irAEs due to ICBT in patients from a single centre of Northern Spain. MethodsWe set up an observational study of patients treated in monotherapy with ICBT targeted against cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1) or its ligand (PD-L1) for solid organ tumours. All patients were followed up in a single University Hospital from March 2015 to September 2018. ResultsWe studied 102 patients (63 men/39 women); mean age 60.6±9.7 years, with lung (n=63), melanoma (n=21), kidney (n=11), gastric (n=3), colon (n=3) or bladder (n=1) cancer. Only 7 patients had a previous diagnosis of an immune-mediated disease, specifically: psoriasis (n=2), psoriatic arthritis (n=1), systemic lupus erythematosus (n=1), spondyloarthitis (n=1), rheumatoid arthritis (n=1) and cutaneous lupus (n=1). One of the following ICBT was administered: nivolumab (n=52), pembrolizumab (n=35), atezolizumab (n=10) and ipilimumab (n=5). After a mean follow-up time of 14.4±7.7 months since ICBT onset, 87 (85.3%) patients had experienced irAEs, mostly gastrointestinal, thyroid and musculskeletal manifestations including inflammatory arthralgia (n= 8), arthritis (n= 6) and myositis (n=2). ICBT was discontinued in 41 patients but it was reintroduced in 30 of them after resolution of the adverse event, with a good tolerance in all cases. Thirty-six (41.4%) of the 87 patients required specific treatment (prednisone, levothyroxine, and thiamazol) for the irAEs. Conclusion irAEs are frequent in patients undergoing ICBT. Almost half of the patients that have irAEs require treatment.Musculoskeletal manifestations are not uncommon.

Myositis in Germany: epidemiological insights over 15 years from 2005 to 2019

“…However, due to the ICD codes used, secondary myositis syndromes were also classified as “other myositis”, as there are overlaps in the coding (e.g., G72.0 Drug-induced myopathy). However, in light of the rarity of these secondary causes [ 17 – 19 ], it can be assumed that the present data are only slightly influenced by this classification of “other myositis”. The increasing prevalence of myositis in older age shown in recent years may be explained, regarding the discrepancy with previous work, by increasing life expectancy [ 11 ].…”

Rheumatic Immune-Related Adverse Events due to Immune Checkpoint Inhibitors—A 2023 Update

“…In parallel with their success against malignancies, ICIs induce potentially severe and even lethal side effects called irAEs, which are considered off-target tissue damage and involve essentially every organ system [ 17 ]. A wide range of irAEs have been described [ 34 , 35 ], including hypophysitis, thyroiditis, myocarditis, pneumonia, pancreatitis, hepatitis, nephritis, adrenal insufficiency, enteritis, and skin rash ( Figure 1 ). Although the underlying mechanisms of irAEs are not fully understood, (1) aberrant cytotoxic T cell activation, (2) increased autoantibody production, (3) direct molecular mimicry, (4) inflammatory cytokine production, (5) complement-mediated inflammation, (6) imparted regulatory T cell function, and other mechanisms contribute to the immunopathology of irAEs [ 17 , 19 , 36 , 37 , 38 ].…”

An Unusual Presentation of Inflammatory Shoulder Arthritis Associated with Nivolumab

“…These agents modify the cell growth cycle and demonstrate versatility in the management of malignancies. Because ICIs disrupt regulatory elements of the immune system, they are associated with a number of immune-related adverse events (irAEs), especially when multiple agents are used simultaneously 1 . These toxic effects may affect any organ and can be fatal 2 .…”