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Optimizing Checkpoint Inhibitors Requires Careful AE Management

Caroline Seymour
Published: Thursday, Aug 30, 2018

Jarushka Naidoo, MBBCh

Jarushka Naidoo, MBBCh
Although the incidence of immune-related adverse events (irAEs) tends to be under 30%, it is imperative for both clinicians and patients to recognize and manage them following treatment with checkpoint inhibitors, explained Jarushka Naidoo, MBBCh.

on Advanced Non–Small Cell Lung Cancer, Naidoo discussed the toxicities associated with the use of immunotherapy in oncology, optimal methods of managing them, and the growing body of knowledge on why they occur.

OncLive: What should physicians know about the management of irAEs?

Naidoo: In my presentation, I spoke about managing the side effects of immunotherapy, or what we call irAEs. I also explored some of the mechanisms of why these toxicities occur and how we can best diagnose and manage them. This has become a more relevant question as more immunotherapeutic agents, specifically checkpoint inhibitors, have been FDA approved across multiple solid and hematologic malignancy indications. It's also more common to develop irAEs when patients receive combination immunotherapy. Now, these are licensed in a number of tumor types, even outside of melanoma. It is even more relevant for clinicians to be able to diagnose and manage patients with these toxicities.

What are the most commonly seen irAEs?

We can separate the most common toxicities [based on patients] who develop general toxicities, which may or not be immune related. These included tiredness, nausea, skin rash, and itch. Then, there are irAEs of interest. We know that these AEs are implicated in the mechanism of action of the drugs. These include thyroiditis, hypophysitis, pneumonitis, and colitis. You can get an "itis" or an inflammation from nearly any organ system in your body.

What should trigger a warning sign for physicians?

Because the AEs of immunotherapy can be so varied, providers need to be aware that any change in the clinical condition of their patients that is different from when they started the immunotherapy could be immune related. Thankfully, the overall incidence of irAEs is low. The incidence is about 5% or less with single-agent immunotherapy drugs and around 10% for some combinations. However, the incidence of severe irAEs with the combination of ipilimumab (Yervoy) and nivolumab (Opdivo) can be upwards of 30%.
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