According to a recent article in PubMed, immune checkpoint inhibitors (ICIs) are the most commonly used type of cancer immunotherapy. ICIs have brought about a substantial improvement in the prognosis for advance stage cancers.
However, they also present an enormous array of immune-related adverse events including rheumatologic disease.
Damage due to inflammation and activation caused by ICIs can affect many organ systems.
Fatalities due to toxicities are rare but may occur. Therefore, patients should be closely monitored.
ICI’s Mechanism of Action
Immune checkpoint inhibitors are a type of antitumor drug that blocks checkpoints (proteins) which function as part of a normal immune system.
Checkpoints play an important role in preventing an immune response that is so strong it kills healthy cells.
Despite the beneficial role of checkpoints, the downside is that they can also interfere with T cells and prevent the T cells from killing cancer cells.
When checkpoints and their partner proteins bind together, an “off” signal is sent to the T cells. This is the downside of checkpoints that prevents the immune system from destroying the cancer cells.
Immunotherapy drugs, ICIs, prevent the binding of checkpoint proteins with other proteins. Therefore the “off” signal remains silent and the T cells are able to destroy the cancer cells.
About Immune Checkpoint Inhibitors
ICI’s were initially approved to treat metastatic melanoma. Since that time, many more indications have been approved for advanced malignancies.
Pembrolizumab (Keytruda), Nivolumab (Opdivo), and Cemiplimab (Libtayo) are just a few of the approved ICIs.
It has been noted that ICIs may cause off-target tissue damage. This is known as immune-related adverse events. The cause, as discussed earlier, is their interference with T cell performance. The results vary in accordance with the organ systems that are involved.
Working with Numbers
There are many ways to code symptoms or clinical findings when collecting data from clinical trials that include oncology (i.e. joint effusion, arthritis).
Rheumatologic adverse events related to checkpoint inhibitors have seldom been reported. Data on rheumatologic adverse events are even more limited.
Therefore, it is necessary to estimate the number of patients needing disease management.
Estimates for the number of patients who would need rheumatologic management for preexisting autoimmune diseases, symptoms of other autoimmune diseases, or flareups of their disease would be about seventy-one percent.
It is recommended that oncologists screen patients periodically when they receive ICIs. If there is evidence of new inflammatory musculoskeletal symptoms that persist, it may be necessary to consult with a rheumatologist.