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New Guidelines for Immunotherapy Use in Lung Cancer

Although immune checkpoint inhibitors (ICIs) have improved patient outcomes in many clinical settings and are considered the standard of care in the treatment of several cancers, their use is also accompanied by the risk of immune-related adverse events. 

To help shed light on the management of these adverse events, the Society for Immunotherapy of Cancer (SITC) recently convened an expert panel to develop clinical practice guidelines to assist medical professionals with clinical decision-making and improving outcomes for patients.

Reporting in the Journal for ImmunoTherapy of Cancer, panel chairs Julie R. Brahmer, MD, MSc, and Marc S. Ernstoff, MD, said that while some immune-related adverse events demand organ-specific management considerations, there are certain overarching management principles that apply to all ICI-related toxicity. 

While many immune-related adverse events resolve upon interruption of therapy and/or treatment with immunosuppressive agents, patients that do not respond to first-line interventions should be managed in consultation with various specialties as needed. 

Organ-specific recommendations for managing immune-related adverse events include patient selection and risk factors, expected timing, terminology, management, and the possibility of overlapping toxicity. 

Given the likelihood of autoimmune flare-ups among individuals with pre-existing autoimmune disorders, the guidelines recommend that clinical decision-making on the use of ICIs should carefully consider the potential consequences of autoimmune disease exacerbation and the potential benefits of ICI treatment in this patient population. 

Studies have found several potential risk factors associated with increased incidence of immune-related adverse events, including: 
• the presence of thymic tumors;
• elevated body mass index;
• specific human leukocyte antigen (HLA) genotypes; and 
• baseline deviations from normal ranges in the levels of such cytokines as interleukin (IL)-6 and IL-17. 

Treating immune-related adverse events differs markedly from that of conventional cancer therapies, and generally comprises immunosuppression with corticosteroids or other immunosuppressive agents. 

Patients experiencing immune-related adverse events may also undergo symptomatic treatments and withholding of ICI dose and/or permanent treatment discontinuation, as dictated by the grade of the adverse event and symptom resolution, as clinically appropriate. 

Consultation with a specialist is recommended in cases of severe toxicities. Unlike conventional chemotherapy or molecularly targeted therapy, there is no known role for ICI dose reduction in managing immune-related adverse events.

Second-line immunosuppressive therapy should be considered in patients who do not respond to initial corticosteroid therapy, though such use also carries potential risks. 

The guidelines also draw attention to what they call a ‘notable group of immune-related adverse events’ due to their high mortality rate – myositis, myocarditis, and myasthenia gravis – which are often seen in the same patients. 

Therefore, suspicion of one or more of these immune-related adverse events should prompt evaluation for all three. Clinicians should consider a baseline electrocardiogram in patients at a higher risk for myocarditis; baseline troponin testing may provide information for evaluating potential future cardiac toxicity.

The panel concluded that the same mechanisms that underpin the effective anti-tumor properties of ICIs may also cause unique toxicities, specifically immune-related adverse events. Given this reality, there is a demonstrated need for clear guidance on the recognition and management of immune-related adverse events. 

“Ideally,” the authors wrote, “future research will continue to improve the management of ICI-induced toxicity and result in improvements to standardized protocols for their diagnosis, monitoring, and resolution. As the field evolves, these guidelines may be updated.”


By Mike Vlessides

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