{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:05:59Z","timestamp":1784246759334,"version":"3.55.0"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Novel agents targeting immune checkpoints are under development to overcome resistance to PD-1\/PD-L1 and CTLA-4 blockade. Incidences of immune-related adverse events (irAEs) and toxicity profiles of novel agents remain unelucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched PubMed\/MEDLINE, Embase, and Web of Science for clinical trials evaluating agents targeting co-inhibitory (B7-H3, CD47, TIGIT, LAG-3, and TIM-3) or co-stimulatory checkpoints (OX40, 4-1BB, CD27, ICOS, GITR, CD70, and CD40) in solid tumors. Incidences of any-grade and grade 3-5 (G3-5) treatment-related AEs (trAEs) and irAEs were extracted from phase 2 and 3 trials, and phase 1\/2 trials with safety information reported at the recommended phase 2 dose. Odds ratios (ORs) from 2-arm studies evaluating the addition of LAG-3 or TIGIT blockade to control-arm therapy were pooled, and AE incidences across immunotherapy subtypes were reported using a random-effects meta-analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A systematic review identified 27 clinical trials comprising 3946 patients. The addition of LAG-3 blockade increased G3-5 trAEs (OR = 1.79, 95% confidence interval [CI] = 1.26 to 2.54, P\u2009=\u2009.001), adrenal insufficiency (G3-5: OR = 8.43, 95% CI = 1.04 to 68.37, P\u2009=\u2009.046; any-grade: OR = 4.81, 95% CI = 1.81 to 12.78, P\u2009=\u2009.002) and any-grade arthralgia (OR = 2.07, 95% CI = 1.29 to 3.30, P\u2009=\u2009.002). Adding TIGIT blockade increased any-grade rash (OR = 2.32, 95% CI = 1.01 to 5.34, P\u2009=\u2009.048). Meta-analyses revealed varying irAE patterns: G5 trAEs (0.9%-2.9%), G3-5 pneumonitis (0.5%-5.5%, highest in TIM-3), G3-5 colitis (0.2%-5.4%, highest in LAG-3), G3-5 hepatitis (1.5%-5.5%, highest in TIM-3), and G3-5 adrenal insufficiency (1.7%-8.4%, highest in TIGIT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study highlights the distinct toxicity profiles of novel immunotherapy agents, providing essential safety data to support clinicians as these therapies approach approval.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jncics\/pkag066","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T11:18:36Z","timestamp":1781695116000},"source":"Crossref","is-referenced-by-count":1,"title":["Safety of immune checkpoint modulators beyond PD-1\/PD-L1 and CTLA-4 in solid tumors: a meta-analysis"],"prefix":"10.1093","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1406-2352","authenticated-orcid":false,"given":"Yu","family":"Fujiwara","sequence":"first","affiliation":[{"name":"Department of Medicine, Roswell Park Comprehensive Cancer Center , Buffalo, NY,","place":["United States"]},{"name":"Department of Clinical Oncology, Institute of Science Tokyo , Tokyo,","place":["Japan"]},{"name":"Department of Medicine, University at Buffalo , Buffalo, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yui","family":"Okamura","sequence":"additional","affiliation":[{"name":"College of Medicine, School of Medicine and Health Sciences, University of Tsukuba , Tsukuba,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mrinalini","family":"Ramesh","sequence":"additional","affiliation":[{"name":"Department of Medicine, University at Buffalo , Buffalo, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin Fakhari","family":"Tehrani","sequence":"additional","affiliation":[{"name":"Department of Medicine, University at Buffalo , Buffalo, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7439-5615","authenticated-orcid":false,"given":"Riona","family":"Aburaki","sequence":"additional","affiliation":[{"name":"Yokohama City University, Yokohama City University School of Medicine , Yokohama,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0364-539X","authenticated-orcid":false,"given":"Toshiaki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Medicine, John A. Burns School of Medicine, University of Hawai\u2019i , Honolulu, HI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manmeet S","family":"Ahluwalia","sequence":"additional","affiliation":[{"name":"Miami Cancer Institute, Baptist Health South Florida , Miami, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2153-3896","authenticated-orcid":false,"given":"Sarbajit","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Miami Cancer Institute, Baptist Health South Florida , Miami, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"2026071619513705400_pkag066-B1","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1016\/j.cell.2023.03.006","article-title":"Immune checkpoint therapycurrent perspectives and future 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