{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:25:48Z","timestamp":1790717148312,"version":"4.1.0"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["5KL2TR002387-05"],"award-info":[{"award-number":["5KL2TR002387-05"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The impact of steroid-sparing immunosuppressive agents (SSIAs) for immune-related adverse events (irAEs) on tumor outcome is not well-known. This systematic review evaluates tumor outcomes for corticosteroid (CS) monotherapy versus CS with SSIA (CS-SSIA) for irAE treatment with a focus on melanoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Search was conducted through 1\/5\/23 using PubMed, Embase, Cochrane CENTRAL, and Web of Science. We included case series, retrospective\/prospective observational studies and interventional clinical trials. Individual-level data was analyzed using KM curves and Cox regression for overall survival (OS) and progression free survival (PFS). Time to SSIA was treated as a time-varying exposure using landmark analysis (landmark timepoint=3 months after irAE) to account for immortal time bias. For group-level data, meta-analysis compared the use of SSIA to No SSIA for irAEs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of twenty-two publications with individual-level data, 147 patients with any cancer (57 CS, 90 CS-SSIA) and 65 with melanoma (18 CS, 47 CS-SSIA) underwent landmark analysis. Twenty-two publications underwent group-level evaluation and four were included in the meta-analysis. CS-SSIA versus CS showed higher risk of all-cause mortality and progression (HR 2.75, 95%CI: 1.44-5.27, p&amp;lt;0.01 and HR 1.75, 95%CI: 1.07-2.85, p=0.03, respectively). Melanoma showed worse OS and PFS for CS-SSIA versus CS (HR 5.68, 95%CI: 1.31-24.67, p=0.02 and HR 2.68, 95%CI: 1.12-6.40, p=0.03, respectively). In the meta-analysis of group-level data (n=2558), we found worse OS and PFS for CS-SSIA versus No SSIA (HR 1.58, 95%CI: 1.25; 2.01, p&amp;lt;0.01 and 1.70, 95%CI: 1.25-2.33, p&amp;lt;0.01). Tumor necrosis factor-alpha inhibitors (TNFi) were the most common SSIA. In the melanoma cohort, TNFi had worse OS and PFS versus CS (HR 6.46, 95%CI: 1.43-29.19, p = 0.02 and HR 7.49, 95%CI: 2.29-24.48, p&amp;lt;0.01, respectively). TNFi versus Other SSIAs showed a trend toward worse OS and worse PFS (HR 6.96, 95%CI: 0.90-53.65, p=0.06 and HR 21.5, 95%CI: 2.63-175.8, p&amp;lt;0.01, respectively). Meta-analysis showed a concern for TNFi compared to Other SSIA (HR 1.56, 95%CI: 1.17-2.09, p&amp;lt;0.01 respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>While our results raise concern about the effects of CS-SSIA and TNFi for irAE therapy on tumor outcomes, prospective randomized controlled trials are needed to definitively assess the effect of SSIAs on tumor outcomes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1499478","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T05:10:45Z","timestamp":1734325845000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Impact of steroid-sparing immunosuppressive agents on tumor outcome in the context of cancer immunotherapy with highlight on melanoma: a systematic literature review and meta-analysis"],"prefix":"10.3389","volume":"15","author":[{"given":"Jennifer","family":"Strouse","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karmela Kimi","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Baccile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gong","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana K. 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