Multiple immunosuppressive therapies increase infection risks for cancer patients

Retrospective analysis of more than 20,000 patient records identifies opportunities for risk-mitigating approaches in certain patient populations.

Immune checkpoint inhibitors (ICIs) can promote antitumor responses but can also cause adverse effects that require treatment with immunosuppressive drugs. A new retrospective study by Mass General Brigham Cancer Institute investigators found that patients who received ICIs and multiple immunosuppressive therapies were at higher risk of serious infections. Nearly half of infections were severe, life-threatening or fatal infections. Results are published in JNCCN-Journal of the National Comprehensive Cancer Network.

Complications from infection may adversely impact quality of life, disrupt cancer-directed therapies, lead to hospitalizations, or even result in death. Our study identifies patient populations for whom these risks might be mitigated with improved screening, monitoring, preventative or preemptive treatment approaches."

Ross Merkin, MD, lead author, medical oncologist, Mass General Brigham Cancer Institute

Patients receiving treatment for cancer may receive multi-agent immunosuppressive therapy (IST) to treat severe autoimmune complications of ICIs, known as immune-related adverse events. However, there is a lack of evidence on how IST affects the risk of opportunistic infections (such as herpesviruses, certain bacteria, or invasive fungi) and non-opportunistic infections (all other pathogens) in high-risk patients with solid tumors who experience these severe autoimmune complications.

The research team characterized infection risk in a cohort of 20,930 patients who received ICI therapy and at least one immune-related adverse event requiring progressively more intense immunosuppression between June 2011 and February 2024. Within this cohort, 142 patients received at least one steroid and two non-steroidal ISTs for treatment of an immune-related adverse event. More than half of this subgroup of patients (52%) experienced either opportunistic or non-opportunistic infections.

Treatment with multiple ISTs was associated with increased rates and severity of infection. Opportunistic infections were more likely when more than two ISTs were administered and were most commonly caused by cytomegalovirus. The researchers determined that patients aged 65 and higher were at greater risk of opportunistic infections, while those with cardiac immune-related adverse events were more susceptible to non-opportunistic infections.

The authors note that further research in larger cohorts is needed to help validate screening strategies and preemptive measures to reduce serious infectious complications in heavily immunosuppressed patients.