{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:03:06Z","timestamp":1790265786419,"version":"4.1.0"},"reference-count":52,"publisher":"Harborside Press, LLC","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,24]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    The use of multiagent immunosuppressive therapy (IST) to treat immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) increases the risk of infection. Time-normalized infection rates in a large cohort have not been previously reported. Predictors of opportunistic and nonopportunistic infections (OIs and non-OIs, respectively) and infection severity are poorly understood.\n                    <jats:bold>Methods:<\/jats:bold>\n                    We conducted a retrospective chart review of patients treated with ICIs and identified those who received simultaneous multiagent IST for irAE treatment, defined as at least 1 supraphysiologic-dose corticosteroid (steroid) and 2 steroid-sparing ISTs administered within 90 days of one another. Patients who received \u22642 ISTs were not included in the analysis. Total exposure duration and the number of OIs and non-OIs occurring during ICI alone, 1 IST, 2 ISTs, and \u22653 ISTs were used to calculate infection rates per 1,000 exposure-days. Significance was assessed using the Poisson test. The cumulative incidence function and Fine-Gray test were applied to identify clinical features associated with infection risk.\n                    <jats:bold>Results:<\/jats:bold>\n                    Between June 2011 and February 2024, 20,930 patients received ICI therapy. A total of 142 (0.68%) patients received 3 ISTs and were included in the analysis. Among the 142 patients, 74 experienced a total of 152 infections, including 132 non-OIs in 68 patients and 20 OIs in 17 patients. Cytomegalovirus reactivation accounted for 10 of 20 OIs. Per 1,000 patient-days, the OI density was 0 during ICI alone, 0.06 with 1 IST, 0.57 with 2 ISTs, and 0.42 with \u22653 ISTs (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;.0001). The corresponding non-OI densities were 0.85, 0.90, 2.04, and 4.14, respectively (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;.0001). When mild and moderate infections were omitted, the same trend was observed. In subgroup analyses, age &gt;65 years was a predictor of OIs (\n                    <jats:italic>P<\/jats:italic>\n                    =.046) but not non-OIs, whereas cardiac irAEs were a predictor of non-OIs (\n                    <jats:italic>P<\/jats:italic>\n                    =.018) but not OIs.\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    These data support the development of improved strategies for infection screening, prophylaxis, and monitoring in patients receiving multiagent IST for irAE treatment.\n                  <\/jats:p>","DOI":"10.6004\/jnccn.2026.7068","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:13:56Z","timestamp":1790262836000},"page":"1-8","source":"Crossref","is-referenced-by-count":0,"title":["Triplet Immunosuppression for Immune Checkpoint Inhibitor\u2013Related Adverse Events is Associated With High Infection Risk"],"prefix":"10.6004","author":[{"given":"Ross D.","family":"Merkin","sequence":"first","affiliation":[{"name":"Mass General Brigham Cancer Institute, Boston, MA"},{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA"},{"name":"Massachusetts Eye and Ear, Boston, MA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan L.","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Restifo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherin J.","family":"Rouhani","sequence":"additional","affiliation":[{"name":"Mass General Brigham Cancer Institute, Boston, MA"},{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Pantano","sequence":"additional","affiliation":[{"name":"Harvard T.H. Chan of Public Health, Bioinformatics Core, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew M.","family":"Lei","sequence":"additional","affiliation":[{"name":"Mass General Brigham Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyre","family":"Zubiri","sequence":"additional","affiliation":[{"name":"Mass General Brigham Cancer Institute, Boston, MA"},{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yevgeniy R.","family":"Semenov","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maysa","family":"Vilbert","sequence":"additional","affiliation":[{"name":"Mass General Brigham Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan L.","family":"Peacker","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Blum","sequence":"additional","affiliation":[{"name":"Mass General Brigham Cancer Institute, Boston, MA"},{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Dennis","sequence":"additional","affiliation":[{"name":"Dana-Farber Brigham Cancer Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth I.","family":"Buchbinder","sequence":"additional","affiliation":[{"name":"Dana-Farber Brigham Cancer Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah P.","family":"Hammond","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry L.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Mass General Brigham Cancer Institute, Boston, MA"},{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4047","reference":[{"key":"B1","series-title":"JAMA Oncol","first-page":"1008","article-title":"Treatment-related adverse events of PD-1 and PD-L1 inhibitors in clinical trials","volume":"5","author":"Wang Y","year":"2019","unstructured":"Wang Y, Zhou S, Yang F,  Treatment-related adverse events of PD-1 and PD-L1 inhibitors in clinical trials. 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