Strategies Proposed to Improve Management of Immune-Related Adverse Events

In a paper published in the Journal for ImmunoTherapy of Cancer, researchers investigators proposed a variety of strategies seeking to improve the management of immune-related adverse events (irAEs) brought on by immune checkpoint inhibitors.

Distinct from conventional cancer treatments that act on tumor growths directly, immune checkpoint inhibitors work by restoring the suppressed immune system in order to attack tumor cells. Nonetheless, by disrupting the homeostatic mechanisms that balance immune cell functions, immune checkpoint inhibitors prompt irAEs in a significant proportion of patients.

Though the majority of irAEs can be managed with immunosuppressive treatments, life-threatening and sometimes fatal events have still been known to occur in patients receiving these therapies. Moreover, without predictive biomarkers to determine which patients are at risk for irAEs or standardized approaches for detection, reporting, and treatment of irAEs, management has proven challenging. These factors taken together suggesting a need to develop strategies that will improve the handling of irAEs.

Importantly though, the incidence of irAEs is largely dependent on the type of immune checkpoint inhibitor used; for example, patients treated with the CTLA-4 inhibitor ipilimumab (Yervoy) experience irAEs at a rate of up to 70% versus around 30% for those treated with a PD-1 inhibitor. The highest incidence of events has been reported in those receiving the CTLA-4/PD-1 inhibitor combination of ipilimumab plus nivolumab (Opdivo). Similarly, the severity and type of irAEs differs with each checkpoint inhibitor used.

“With increasing use of [immune checkpoint inhibitors] for treatment of various cancers, the incidence of irAEs will undoubtedly increase,” the study authors who were led by Aung Naing, MD, wrote in their paper. “There is a compelling need to develop measures to effectively manage irAEs, both in the community settings and in cancer centers alike.”

In order to address the current unmet need in this area, investigators recommended a variety of measures for the effective management of irAEs including. Strategies recommended for the effective management of irAEs included:

• Implementing patient education resources tailored to the individual needs of the patient in order to enhance awareness and thoughtful conversation
• Clarifying guidelines for the management of irAEs and regularly convening a summit to revise the guidelines as needed
• Adding more terms to the Common Terminology Criteria for Adverse Events (CTCAE) for standardized capture of all irAEs
• Optimizing the choice, dosing, and duration of use of immunosuppressive agents for the management of irAEs
• Seeking to better understand irAEs and their possible association with treatment outcomes through more preclinical, translational, and clinical studies
• Incorporating high-risk patients into studies of immune checkpoint inhibitors and establishing a national registry of these patients
• Integrating the use of diagnostic tools to personalize the management of irAEs and aid in facilitating decision making
• Equipping health care providers with wireless technology and digital resources
• Producing a platform to ensure the missing patient’s voice is heard
• Disseminating evolving data to the scientific community promptly in order to expedite the translation of research results

“By adopting strategies such as listening to patients’ voices, conducting preclinical, clinical, and translational studies to identify predictive markers of irAEs, and developing evidence-based irAE management guidelines, we can minimize the toxic effects of [immune checkpoint inhibitors] while achieving the full therapeutic potential of these drugs,” concluded the authors.

Reference:

Naing A, Hajjar J, Gulley JL, et al. Strategies for improving the management of immune-related adverse events. Journal for ImmunoTherapy of Cancer 2020;8(2):e001754. doi:10.1136/jitc-2020-001754