Dutch researchers have explored the frequency and outcomes of ICI-associated immune-related adverse events in people with cancer.
Immune-related adverse events leading to ICU admissions in cancer patients appears to be a price worth paying, according to new research.
Immune checkpoint inhibitors have revolutionised the treatment of cancer. But their distinct mechanisms of action – targeting the programmed death (PD-1) ligand and the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) receptor – are somewhat of a double-edged sword, as their use is also associated with severe, life-threatening immune-related adverse events requiring patients to be admitted to the ICU.
Despite the known severity of these immune-related adverse events, little is known about the outcomes of cancer patients who are admitted to the ICU as a result of these events. But a new systematic review, published in Cancer Treatment Reviews, has examined the literature to better understand the potential outcomes of patients in this cohort.
“With the expanding use of ICIs for the treatment of solid tumours in clinical practice, life-threatening immune-related adverse events in need of ICU admission are becoming more common and early treatment on the ICU can often be lifesaving,” the researchers wrote.
“Based on the favourable outcomes after life-threatening immune-related adverse events, ICU admission should definitely be considered for patients with solid tumours who have life-threatening immune-related adverse events”.
The researchers included 183 articles in their review: six ICU population-based studies (four of which were retrospective) involving 169 patients admitted to the ICU as a result of immune-related adverse events, 25 retrospective studies describing immune-related adverse events in patients with an incidental ICU admission, 153 case reports/series of 177 cases and a solitary review of previously published case reports.
The greatest emphasis was placed on the results of the population-based studies, where pneumonitis and neurological immune-related adverse events – including, but not limited to, encephalitis, meningitis, myelitis and myasthenia gravis – were the most frequently reported events (28% and 20% of patients, respectively). One in four of the 169 patients in the population-based studies died in the ICU, with a further 8% dying within the following three to six months.
Pneumonitis also occurred frequently in the case reports and series and had the highest mortality rate after ICU admission (53%), ahead of other adverse events such as myasthenia-myositis (50%) and cardiovascular-related events (35%).
The case reports and series also revealed that pneumonitis was more common after patients received a combination of ICI therapies (i.e. both an anti-CTLA-4 and anti-PD-1 treatment) compared to patients who received monotherapy.
Related
Stopping ICI therapy after the appearance of immune-related adverse events appears to have more positives than negatives, according to the researchers.
“Although severe immune-related adverse events often require discontinuation of treatment with ICIs, early discontinuation of ICIs does not affect the cancer specific outcome,” they noted.
“In particular, there are indications that the development of (severe) immune-related adverse events is associated with improved cancer specific overall survival. This [survival] benefit sustains when second-line immunosuppressive agents are administered, even while these agents may contribute to a poorer cancer specific outcome.”
The researchers highlighted the need to develop predictive models and guidelines around the process of managing patients who experience immune-related adverse events while (or after) being treated with immune checkpoint inhibitors, as they anticipate the treatment approach will continue to become more common over time.
“Managing critically ill patients with solid tumours, oncologists and intensivists are often challenged by clinical and ethical dilemmas and choosing the most suitable treatment,” they concluded.
“There are no guidelines to select patients with life-threatening immune-related adverse events for admission to the ICU and the perception of oncologists in managing these patients may differ.
“However, the potential favourable outcomes of both the solid tumours and the immune-related adverse events will probably result in more ICU admissions due to severe immune-related adverse events. Therefore, prognostic models could be useful to guide the decision to admit patients with severe immune-related adverse events to the ICU.”
