Checkpoint inhibitors may cause irAE in many cancer patients

By Selina Wellbelove

6 Sep 2021

Immune checkpoint inhibitors (ICI)  have been linked with a high rate of immune related adverse events (irAE) in cancer patients.

Smokers and patients of older age were found to be at particular risk, suggests an analysis led by Dr Margaret M. Byrne, a haematologist and oncologist at Tufts Medical Center in the US, and published in the European Journal of Haematology.

The study population included patients receiving ICIs for lung cancer (50%), genitourinary cancer (15%), head and neck squamous cell cancer (14%), melanoma (11%) and lymphoma (2%). The most commonly used ICIs were nivolumab (44%) pembrolizumab (44%) and atezolizumab (8%).

Of 131 patients treated with an ICI at Tufts Medical Center in Boston between 2014 and 2018, researchers found that 43.5% developed at least one irAE and that 33% developed two or more. The median time to initial irAE was 250 days, and the most common were dermatitis (21.4%), thyroid dysfunction (17.6%) and pneumonitis (9.9%).

The majority of immune related side effects recorded during the period were found to be mild-to-moderate in nature, with 31.6% categorised as grade 1, 52.6% as grade 2, and 15.8% as grade 3 or 4, though none resulted in death.

Also, while in most (63.2%) affected patients the adverse event was resolved, 41.7% experienced a recurrent irAE, 80% of which occurred at a new site and 40% of which were classed as high grade.

The authors highlighted smoking and older age as possible predictors of irAE; their multivariable analysis showed that patients aged over 65 years were 1.8 times more likely and those who smoked 2.3 times more likely to develop an irAE.

While there were key limitations to the study, including a relatively small sample size and heterogeneous patient population, its findings are important as they add to current understanding of the toxicities linked with ICI, particularly in the real world setting, which is limited, according to the paper.

Given that the clinical indications of ICI therapy “expanded dramatically” during the study period, the authors have called for further research using more current patient populations “to help guide clinical decision-making”.

However, they also noted that “it may become more difficult to tease apart the side effects specific to ICI therapies in the future”, as their use expands alongside chemotherapy and other targeted treatments.

Pembrolizumab (Keytruda) and nivolumab (Opdivo) are currently approved in Australia for the treatment of cancers such as melanoma, NSCLC, HNSCC and also some lymphomas.

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