Early detection of immunotherapy-mediated toxicity

The number of tumor types and settings in which immune checkpoint inhibitors
(immunotherapy) is standard treatment is rapidly expanding. However, toxicity
is a frequent adverse event often necessitating high-dose of immunosuppressant
treatments such as corticosteroids and sometimes even requiring permanent
discontinuation of checkpoint inhibitors. Early detection of
immunotherapy-mediated toxicity and early initiation of immunosuppressant
treatment might reduce the total dose of glucocorticoids and other
immunosuppressants needed for clinical management. More importantly, it might
result in a lower discontinuation rate of treatment due to severe toxicity.

We hypothesize that during an episode of immune-mediated organ specific
toxicity, as a result of inflammation and damage to the specific organ,
organ-derived DNA will be detectable in blood of patients. The aim of this
project is to investigate whether the presence of cell-free DNA originating
from the organ towards which immunotherapy-induced toxicity is directed, can be
detected using epigenetic profiling of cell-free DNA.

Organ specific methylation patterns in cell-free DNA will be derived from 1)
paired blood samples collected from patients during an episode of
immunotherapy-mediated toxicity and in absence of immunotherapy-mediated
toxicity and 2) samples from patients without checkpoint inhibitor treatment
but with organ confined auto-immune diseases. Optionally, feces will be
collected at the same time points to investigate inflammation biomarkers during
an episode of immunotherapy-mediated colitis. In addition, blood will be drawn
for investigation of other biomarkers of inflammation.

The risk of blood withdrawals is negligible.