{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:42:26Z","timestamp":1765546946286,"version":"3.41.2"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Standard combination ipilimumab\/nivolumab (I\/N) is given as 4 induction doses for advanced stage melanoma followed by nivolumab single-agent maintenance therapy. While many patients receive less than 4 doses due to immune-related toxicities, it is unclear if fewer doses of I\/N may still provide long term clinical benefit. Our aim is to determine if response assessment after 1 or 2 doses of I\/N can predict long-term survival and assess if fewer doses of I\/N can lead to similar survival outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a retrospective analysis on a cohort of patients with advanced melanoma who w0ere treated with standard I\/N. Cox regression of progression-free survival (PFS) and overall survival (OS) models were performed to assess the relationship between response after 1 or 2 doses of I\/N and risk of progression and\/or death. Clinical benefit response (CBR) was assessed, defined as SD (stable disease) + PR (partial response) + CR (complete response) by imaging. Among patients who achieved a CBR after 1 or 2 doses of I\/N, a multivariable Cox regression of survival was used to compare 1 or 2 vs 3 or 4 doses of I\/N adjusted by known prognostic variables in advanced melanoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>199 patients were evaluated. Patients with CBR after 1 dose of I\/N had improved PFS (HR: 0.16, 95% CI 0.08-0.33; p&amp;lt;0.001) and OS (HR: 0.12, 0.05-0.32; p&amp;lt;0.001) compared to progressive disease (PD). Patients with CBR (vs PD) after 2 doses of I\/N also had improved PFS (HR: 0.09, 0.05-0.16; p&amp;lt;0.001) and OS (HR: 0.07, 0.03-0.14; p&amp;lt;0.001). There was no survival risk difference comparing 1 or 2 vs 3 or 4 doses of I\/N for PFS (HR: 0.95, 0.37-2.48; p=0.921) and OS (HR: 1.04, 0.22-4.78; p=0.965).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Early interval imaging with response during induction with I\/N may be predictive of long-term survival in advanced stage melanoma. CBR after 1 or 2 doses of I\/N is associated with favorable survival outcomes, even in the setting of fewer I\/N doses received. Further studies are warranted to evaluate if electively administering fewer combination I\/N doses despite tolerance in select patients may balance the benefits of therapy while decreasing toxicities.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.860421","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T04:38:26Z","timestamp":1657082306000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Early Response Assessment in Advanced Stage Melanoma Treated with Combination Ipilimumab\/Nivolumab"],"prefix":"10.3389","volume":"13","author":[{"given":"Vincent T.","family":"Ma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alahendra A.","family":"Chamila 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