Immune-related adverse events and immune checkpoint inhibitors: a focus on neurotoxicity and clinical management

ABSTRACT

Introduction

Immune checkpoint inhibitors (ICIs) represent an innovative therapeutic approach of oncologic diseases. In Europe, this therapeutic class currently includes eight agents: ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, cemiplimab, durvalumab and dostarlimab. Despite their proved clinical benefits, they can induce immune-related adverse events (irADRs), that can also involve the nervous system.

Areas covered

Despite their rarity, neurological irADRs related to ICI-treatments can lead to serious and dangerous complications, highlighting the importance of a strict monitoring of patients. This review aims to summarize the safety profile of ICIs, focusing on their possible neurotoxicity and their management.

Expert opinion

Considering the clinical relevance of ICIs-induced irADRs and that the underlying mechanisms are still not completely understood, the use of ICIs requires extensive safety monitoring. Before to prescribe immunotherapy, oncologists should identify possible individual risk factors that may favor the onset of irADRs. Oncologists and general practitioners should inform and educate patients about the specific toxicities of immunological checkpoint inhibitors, including nervous ones. They should be carefully monitored at least 6 months after the end of treatment. ICIs-related nervous toxicities require a multidisciplinary management, in which neurologists and clinical pharmacologists should participate.

KEYWORDS:

• Immune-related adverse events
• immune checkpoint inhibitors
• neurotoxicity
• neurotoxicity
• clinical managment

Article highlights

• Immune-related toxicity inducible by immune checkpoint inhibitors (ICIs) frequently requires a multidisciplinary management, in which neurologists and clinical pharmacologists should participate.

• Future research should focus on identifying cancer patients who are at increased risk of developing neurologic immune-related adverse drug reactions (irADRs) when treated with ICI.

• Different ICI-related neurological disturbs have been summarized in this review.

• Central nervous disorders, including infections and inflammations, demyelinating and vascular disorders, occur more rarely compared to peripheral neuropathies.

• ICI-induced Guillain Barré syndrome (GBS) may differ from traditional GBS.

• If not promptly and properly recognized nervous irADRs can be seriously debilitating and life-threatening.

• When other possible causes are excluded, the front-line therapy is represented by corticosteroids.

• Other immune-modulating strategies should be considered for the irADRs management, including biological disease-modifying anti-rheumatic drugs (DMARDs), conventional or target synthetic DMARDs, as well as intravenous immunoglobulin (IVIG) or plasmapheresis.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.