Abstract
Numerous immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), have been approved for the treatment of genitourinary (GU) malignancies. While ICIs have improved treatment outcomes and expanded treatment options, they can cause immune-related adverse events (irAEs). The scope of irAEs is broad, and this paper aims to review the rheumatologic side effects associated with immunotherapy drugs approved for bladder cancer and renal cell carcinoma. IrAEs are graded by the common terminology criteria for adverse events (CTCAE), which ranges from 1 to 5. The management of irAEs includes corticosteroids or other immunosuppressive therapies, and it may require discontinuation of immunotherapy. Several real world experience studies suggest that most patients with pre-existing autoimmune diseases treated with ICI did not have to discontinue treatment due to immune-mediated side effects. While data suggest autoimmune side effects are manageable, patients with pre-existing autoimmune diseases are often excluded from immunotherapy clinical trials. Better understanding of these irAEs will improve its safety and expand its use in those with underlying autoimmune disease.
Highlights
Genitourinary malignancies include primarily the cancers of the prostate, bladder and kidneys, and testicular and penile cancers occur less frequently
These include the programmed cell death receptor 1 (PD-1) inhibitors nivolumab and pembrolizumab, the programmed cell death ligand 1 (PD-L1) inhibitor avelumab, and combination therapies have shown benefits in overall and progression free survival [3–5]. These important benefits of immune checkpoint inhibitors (ICIs) therapy are balanced by a significant risk of “off target” adverse effects, formally known as immune-related adverse events, which occur as a result of unregulated immune activity against non-cancer tissue
One recent study estimates that immune-related adverse events (irAEs) will affect nearly 60% of patients treated with combination ipilimumab and nivolumab [6]
Summary
Genitourinary malignancies include primarily the cancers of the prostate, bladder and kidneys, and testicular and penile cancers occur less frequently. Numerous drugs within the ICI class have been approved for the treatment of kidney, bladder cancer, and other non-GU cancers These include the PD-1 inhibitors nivolumab and pembrolizumab, the PD-L1 inhibitor avelumab, and combination therapies have shown benefits in overall and progression free survival [3–5]. While significant attention has been directed towards characterizing and quantifying the scope of irAEs, comparatively little is known of the rheumatologic side effects of ICIs and the effects of ICIs on patients with pre-existing autoimmune or rheumatologic disease Autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and multiple sclerosis (MS), among many others, are highly prevalent, affecting somewhere between 24 and 50 million people in North America alone. We focus on treatment side effects, both as de novo and as potential flare of pre-existing autoimmune symptoms
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