Evolving terminology regarding cancer immunotherapy side effects (immune-mediated adverse reactions)

What terms should we be using for treatment-related side effects that are associated with various cancer immune checkpoint inhibitor therapy? The NCCN guidelines (developed in partnership with ASCO) are titled, "Management of Immunotherapy-Related Toxicities." ASCO named their guideline, "Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy." 

Over the past few years, many published studies used the term "immune-related adverse events or irAEs."  The SITC toxicity management working group published consensus recommendations using the phrase "immune-related adverse events."  In press releases and news updates, the FDA used phrases like "Infection and immune-related adverse events such as pneumonitis, hepatitis, colitis, thyroid disease, adrenal insufficiency, diabetes, pancreatitis, and dermatitis/rash were also seen with ..."  (At times, the FDA used the term "immune-mediated adverse reactions") 

We may be entering an era where the phrase "irAE" may be going away. It may get replaced with "imAE." 

As of Jan 2019, here is what you will find on the websites of PD-1 and PD-L1 inhibitors:
​

Manufacturer	Description	Websites
AstraZeneca	​Immune-Mediated Adverse Events or imAEs ​Immune-Mediated Adverse Reactions	​https://www.azimmuno-oncology.com/immuno-oncology-in-practice/immunotherapy-side-effects.html ​ https://www.imfinzihcp.com/durvalumab-side-effects.html
​Bristol-Myers Squibb	Immune-Mediated Adverse Reactions	​https://www.immunooncologyhcp.bmsinformation.com/clinical-expectations/adverse-reactions/ ​http://www.opdivohcp.com/ ​http://www.hcp.yervoy.com/
​Genentech	​Immune-Mediated Adverse Reactions	https://www.tecentriq-hcp.com/
​Merck​	​​Immune-Mediated Adverse Reactions	​​https://www.keytruda.com/hcp/adverse-reactions/
END Serono and Pfizer	​​Immune-Mediated Adverse Reactions	​https://www.bavencio.com
Regneron and sanofi-aventis	​Immune-Mediated Adverse Reactions	https://www.libtayohcp.com/

You can find more information about specific immune-mediated adverse reactions such as immune-mediated pneumonitis; immune-mediated hepatitis; immune-mediated colitis; and others.

What is the distinction between immune-related vs. immune-mediated? Let's start by reviewing some definitions:

• One definition for the word "related" states: associated with the specified item or process, especially causally.
• One definition for the word "mediated" states: bring about (a result such as a physiological effect). Webster's definition of "immune-mediated" states: resulting from the activity of the immune system; mediated by the immune response

The link between immune activation and immune-mediated adverse reactions is an active area of ongoing research. 
 
PD-1 and PD-L1 inhibitors approved by the FDA (as of Jan 2019) include:

Target	Drug Name	Brand Name
PD-1	Pembrolizumab	Keytruda
PD-1	Nivolumab	Opdivo
​PD-1	Cemiplimab	Libtayo
​PD-L1	Atezolizumab	Tecentriq
PD-L1	Avelumab	Bavencio
PD-L1	Durvalumab	Imfinzi