Study warns of risks associated with a type of cancer immunotherapy

Treatment with immune checkpoint inhibitors (ICIs) has significantly improved the prognosis for cancer patients, although it can be associated with a wide variety of adverse effects (AEs) affecting multiple organs. An international study on ICIs-related AEs reported in real-world clinical practice has found that the annual frequency has increased between 2012 and 2023, as expected due to the growing use of immunotherapy. However, the mortality rate of reported AEs remains stable at around 25%. By developing an algorithm based on data from more than 290,000 cases reported in total to both the US FDA and the WHO, the study's researchers found that 20% of ICI-related AEs have a high mortality rate. Thirty-six per cent of patients who experienced certain AEs died, compared with 11 per cent of those who experienced other ICI-related AEs. There are 63 highly fatal AEs, including respiratory, cardiac, muscular, vascular, hepatic, and infectious events. Identifying these AEs with high mortality rates can help establish surveillance measures for patients receiving ICIs and improve their management.

This is a retrospective study based on a large amount of pharmacovigilance data on all types of cancer, types of ICIs and types of AEs reported. The methodology is robust, with validation in other databases after the initial analysis. The results reinforce previously described observations (pneumonitis, hepatitis, myositis, etc.) from an epidemiological and global perspective. The main contribution is that it detects AEs with higher mortality, which is very important when assessing the safety and risks of ICI therapy, considering its surveillance and the treatment of these complications.

The main limitations of the study are well covered in the discussion, for example, the fact that among the causes of the high mortality observed, it is not possible to differentiate between those attributed to the cancer itself, the direct effect of the drug, or other derived effects; it reflects overall mortality. In our clinical practice, the results have an impact on various specialities, such as pulmonology, cardiology, hepatology, neurology, and rheumatology, which, together with oncology, we use to care for and treat cancer patients when they present with ICI-related AEs.

This recent study published in PNAS analyzed severe adverse effects related to immune checkpoint inhibitors (ICIs), which are therapies with great promise for cancer treatment. With data from over 290,000 cases of patients treated with ICIs from global pharmacovigilance databases, the researchers applied advanced statistical methods to identify 73 types of organ-specific adverse events with significantly high mortality rates, termed “ICI-related high-mortality AEs”. The most significant ones include liver failure, respiratory failure, and septic shock. This approach, based on robust data and validated methods, also identified emergent complications not reported previously, such as gastrointestinal necrosis and portal vein thrombosis, which represents an important advance in the knowledge about the safety of these drugs. 

The study aligns with previous research that explored the adverse effects of ICIs, but it provides a novel perspective through the analysis of the relationship between these events and mortality rates. However, the authors of the article point out significant limitations in their own work, such as the lack of information about the severity and medical management of the adverse events, the treatment doses, and the specific causes of the reported deaths. Furthermore, the data lack information about patient ethnicity, which could limit the generalization of the results to different populations and clinical scenarios. 

In the context of Spain, where ICIs experience increased use in cancer treatment, this study underlines the importance of proactive surveillance strategies to identify and manage severe adverse events. The recommendation for healthcare professionals is to perform a more exhaustive follow-up of patients treated with ICIs, especially those with a higher risk of severe complications, like liver or respiratory failure. Additionally, the results could serve as a basis to establish formal contraindications for patients with a high risk of fatal adverse events, which would optimize the safety and efficacy of these therapies in clinical practice.