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,” said lead author Ross Merkin, MD, a medical oncologist with the Mass General Brigham Cancer Institute. “Our study identifies patient populations for whom these risks might be mitigated with improved screening, monitoring, preventative or preemptive treatment approaches.”
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.
Authorship: In addition to Merkin, Mass General Brigham authors include Tristan L. Lim, Daniel Restifo, Sherin J. Rouhani, Matthew Lei, Leyre Zubiri, Yevgeniy Semenov, Maysa Vilbert, Bryan L. Peacker, Steven Blum, Sarah P. Hammond, and Kerry L. Reynolds. Additional authors include Lorena Pantano Rubino, Michael Dennis, and Elizabeth I. Buchbinder.
Disclosures: Lei disclosed serving as a consultant for Integra Connect, C4XD, and Center for Business Models; and serving as a scientific advisor for Eli Lilly, Genmab, Genentech, Replimune, and Sanofi. Blum disclosed receiving grant/research support from AstraZeneca and Astellas; serving as a consultant for Two River Consulting Partners; and owning stock or an ownership interest in Kronos Bio, 76Bio, Allogene Therapeutics, and Candid Therapeutics. Hammond disclosed receiving institutional grant/research support from Cidara Therapeutics, F2G, GSK, Mundipharma, and SCYNEXIS; serving as a scientific advisor for Melinta Therapeutics, Pfizer, Roche, Seres Therapeutics, and Treeline Biosciences; and serving on a clinical trial committee for Takeda. Reynolds disclosed receiving institutional grant/research support from Bristol Myers Squibb; and serving as a scientific advisor for Gilead, Regeneron, and UpToDate.
Funding: This work was supported in part by the Pugh Family Research Fund at the Mass General Cancer Center.
Paper cited: Merkin RD et al. “Triplet Immunosuppression for Immune Checkpoint Inhibitor–Related Adverse Events is Associated With High Infection Risk” J Natl Compr Canc Netw DOI: 10.6004/jnccn.2026.7068
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Journal of the National Comprehensive Cancer Network
Observational study
People
Triplet Immunosuppression for Immune Checkpoint Inhibitor–Related Adverse Events is Associated With High Infection Risk
24-Sep-2026
Lei disclosed serving as a consultant for Integra Connect, C4XD, and Center for Business Models; and serving as a scientific advisor for Eli Lilly, Genmab, Genentech, Replimune, and Sanofi. Blum disclosed receiving grant/research support from AstraZeneca and Astellas; serving as a consultant for Two River Consulting Partners; and owning stock or an ownership interest in Kronos Bio, 76Bio, Allogene Therapeutics, and Candid Therapeutics. Hammond disclosed receiving institutional grant/research support from Cidara Therapeutics, F2G, GSK, Mundipharma, and SCYNEXIS; serving as a scientific advisor for Melinta Therapeutics, Pfizer, Roche, Seres Therapeutics, and Treeline Biosciences; and serving on a clinical trial committee for Takeda. Reynolds disclosed receiving institutional grant/research support from Bristol Myers Squibb; and serving as a scientific advisor for Gilead, Regeneron, and UpToDate.