Diagnosis and Management of Rare Immune-Related Adverse Events

Abstract

Oncologic treatment is being revolutionized by a burgeoning number of immune checkpoint inhibitors (ICPis). To date, seven ICPis have received Food and Drug Administration approval, targeting cytotoxic T-lymphocyte antigen, programmed cell death, or programmed cell death ligand. Adverse events associated with checkpoint inhibition have been described in the literature. Guidelines exist for the most common of these, but as the use of ICPis becomes more common, the number of patients presenting with rare events will increase. This article reviews the diagnosis and management of rare ocular, hematological, luminal gastrointestinal, and rheumatological toxicities arising from ICPi treatment. The Oncologist 2020;25:6-14 KEY POINTS• As the use of immune checkpoint inhibitors (ICPis) becomes more common, the number of rare immune-related adverse events (irAEs) will increase. A high level of suspicion is required to identify and treat these toxicities. • Although it can be difficult to definitively attribute rare irAEs to ICPis, a temporal and mechanistic relationship and the absence of other etiologies should make the treating physician suspicious for a rare irAE. • Certain rare irAEs, such as celiac disease, do not require treatment with glucocorticoids. Thus, differentiating this irAE from other gastrointestinal irAEs has important implications for treatment.

Immune checkpoint inhibitor-associated celiac disease

“…[14][15][16] Interestingly, rare cases of patients with de novo elevation of serum tTG antibodies in the setting of treatment with ICIs have been reported. [17][18][19] The nature of the relationship between serum tTG antibodies and ICI-Duo is currently unclear, but it has been hypothesized to reflect treatment-emergent CeD. 17 20 Whether ICI-associated celiac disease (ICI-CeD) reflects new onset gluten sensitivity or is the first manifestation of previously asymptomatic CeD remains an open question.…”

Lessons to be Learnt from Real-World Studies on Immune-Related Adverse Events with Checkpoint Inhibitors: A Clinical Perspective from Pharmacovigilance

“…Overall, the decision to reintroduce the drug(s) should be made on an individual basis. As the use of ICIs becomes more common, the number of rare irAEs will increase, thus making suspicion and differential diagnosis vital for treatment and tailored management strategy [81].…”

Bilateral Posterior Uveitis and Retinal Detachment During Immunotherapy: A Case Report and Literature Review

“…There are several guidelines regarding the management of irAEs, including those published by ESMO, SITC, and ASCO/NCCN ( 47 – 49 ). However, the treatment of rare irAEs such as ocular toxicity is not fully clear due to lack of adequate evidence ( 50 ). NCCN guidelines recommend the use of systemic corticosteroids and tropical steroids as initial treatment ( 47 ).…”